Publications by authors named "Chuifeng Fan"

56 Publications

WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression.

Cell Death Dis 2021 Apr 9;12(4):384. Epub 2021 Apr 9.

Department of Pathology, College of Basic Medical Sciences and the First Affiliated Hospital of China Medical University, Shenyang, China.

WW domain binding protein-2 (WBP2) can function as a Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) co-activator and has a crucial role in promoting breast cancer progression. However, the expression and potential molecular mechanisms of WBP2 in the context of lung cancer are not fully understood. We determined that WBP2 was highly expressed in lung cancer specimens and cell lines and that this expression was closely related to the advanced pTNM stage, lymph node metastasis, and poor prognosis of patients. In addition, gain- and loss-of-function experiments revealed that WBP2 could significantly promote the proliferation and invasion of lung cancer cells both in vivo and in vitro. To elucidate the underlying molecular mechanism, we determined that wild-type WBP2 could competitively bind to the WW domain of WWC3 (WW and C2 domain-containing-3) with LATS1 (Large tumor suppressor-1) through its PPxY motifs, thus inhibiting the formation of the WWC3-LATS1 complex, reducing the phosphorylation level of LATS1, suppressing the activity of the Hippo pathway, and ultimately promoting YAP nuclear translocation. Therefore, from the aspect of upstream molecules of Hippo signaling, WBP2 promotes the malignant phenotype of lung cancer cells in a unique manner that is not directly dependent upon YAP, thus providing a corresponding experimental basis for the development of targeted therapeutic drugs for lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03600-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035140PMC
April 2021

ATF4 promotes lung cancer cell proliferation and invasion partially through regulating Wnt/β-catenin signaling.

Int J Med Sci 2021 29;18(6):1442-1448. Epub 2021 Jan 29.

Department of Pathology, First affiliated hospital and College of Basic Medical Sciences of China Medical University, 110001, Shenyang, China.

Activating transcription factor 4 (ATF4) is a member of the cAMP response element binding (CREB) protein family and has been reported to participate in cancer progression; however, its molecular mechanism is not fully understood. In this study, we investigated the function of ATF4 in non-small cell lung cancer and its molecular regulation. We detected cytoplasmic and nuclear ATF4 expression in lung cancer A549, H1299, and LK2 cells, and the total expression of ATF4 was higher than that in HBE cells ( < 0.05). Higher nuclear ATF4 expression was detected in all these cells compared to cytoplasmic ATF4 expression ( < 0.05). Overexpression of ATF4 in A549 cells significantly promoted cancer cell growth and invasion ( < 0.05). Expression of Wnt signaling molecules, including β-catenin, MMP7, and cyclin D1, and the activity of canonical Wnt signaling were also significantly promoted by ATF4 ( < 0.05). ICG001, a canonical Wnt signaling inhibitor that selectively inhibits β-catenin/ cyclic adenosine monophosphate response element binding protein (CBP) interaction, significantly inhibited cancer cell invasion and Wnt signaling. The function of ATF4 was also significantly inhibited by ICG001 ( < 0.05). However, compared to treatment with ICG001, the invasion ability of cancer cells treated with both ICG001 and ATF4 cDNA significantly increased ( < 0.05), which indicates that the function of ATF4 was not dependent only on Wnt/β-catenin signaling. The function of ATF4 in the regulation of β-catenin expression was not significantly affected by ICG001 ( > 0.05). The function of ATF4 to promote the activity of Wnt/β-catenin signaling in cancer cells was abolished by treatment with ICG001 ( > 0.05). These results indicate that ATF4 may contribute to lung cancer progression at least partly by regulating Wnt/β-catenin signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.43167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893563PMC
January 2021

A retrospective observational study of intraductal breast papilloma and its coexisting lesions: A real-world experience.

Cancer Med 2020 10 21;9(20):7751-7762. Epub 2020 Aug 21.

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.

Background: Breast intraductal papilloma is a heterogeneous group. The aim of the study is to investigate the intraductal breast papilloma and its coexisting lesions retrospectively in real-world practice.

Methods: We retrospectively identified 4450 intraductal breast papilloma and its coexisting lesions.

Results: About 18.36% of intraductal papilloma coexisted with malignant lesions of the breast, 37.33% coexisted with atypia hyperplasia (AH), 25.24% coexisted with benign lesions, and only 19.10% coexisted without concomitant lesions. In addition, 36.80% of intraductal breast papilloma had nipple discharge, 51.46% had a palpable breast mass, and 16.45% had both nipple discharge and a palpable breast mass. About 28.18% experienced discomfort or were asymptomatic. Furthermore, 98.99% had ultrasound abnormalities, and 53.06% had intraductal hypoechogenicity upon ultrasound. 31.89% had mammographic distortion, and 14.45% had microcalcification upon mammography. Intraductal breast papilloma with malignancy had significant correlations with clinical manifestations.

Conclusion: Coexisting malignancy was also related to ultrasound abnormality (BIRADS 4C and 5), mammographic distortion, and microcalcification upon mammography but was not related to the intraductal hypoechoic upon ultrasound. Coexisting atypical hyperplasia correlated with nipple discharge but not palpable mass, mammographic distortion, or intraductal hypoechoic upon ultrasound. The coexisting AH was also related to abnormality upon ultrasound or microcalcification compared with the benign lesions. The intraductal papilloma coexists with malignancy or AH accounted for more than 50%, and the clinical information on papilloma and its coexisting lesions is nonspecific. We recommended surgical treatment for benign intraductal papillary lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571817PMC
October 2020

Ube2S regulates Wnt/β-catenin signaling and promotes the progression of non-small cell lung cancer.

Int J Med Sci 2020 14;17(2):274-279. Epub 2020 Jan 14.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 110001, Shenyang, China.

Ubiquitin conjugating enzyme E2S (Ube2S) plays important roles in cancer development in some malignant tumors. However, the functions and related molecular network of Ube2S in non-small cell lung cancer are not fully understood. In the current study, we examined the expression of Ube2S in non-small cell lung cancer and its clinicopathological significance. We also investigated the molecules and pathways regulated by Ube2S. An immunostaining study showed that the positive rate of Ube2s expression in lung cancer tissues was higher than that in normal lung tissues ( < 0.05). Upregulated Ube2S expression in cancer tissues significantly correlated with clinical progression (TNM III versus I + II), lymph node metastasis, and shorter survival time of the patients ( < 0.05). When Ube2S was overexpressed in A549 cells, the abilities of these cells to proliferate and migrate were increased ( < 0.05). Moreover, Ube2S significantly upregulated the expression of β-catenin, cyclin D1, and MMP7 (novel molecules of the Wnt/β-catenin pathway), and the activity of this pathway ( < 0.05). In addition, a Wnt/β-catenin signaling inhibitor effectively abolished the function of Ube2S. These results indicate that Ube2S may be a novel marker contributing to lung cancer development, possibly through regulating canonical Wnt signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.40243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990889PMC
November 2020

Timescale of tumor volume of a young breast cancer patient with luminal B subtype: A case report.

Medicine (Baltimore) 2019 Oct;98(43):e17659

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.

Rationale: It is largely unknown about the tumor growth of breast cancer naturally. We devised and analyzed an appropriate mathematical tool of the equations that describe how fast tumors grow without treatment on the basis of the ellipsoid shape of solid breast cancer.

Patient Concerns: A 31-year-old woman presented with a painless palpable lump in her left breast for 5 months.

Diagnosis: Infiltrated ductal breast cancer (histologic grade II) of luminal B INTERVENTIONS:: The patient did not receive any therapy due to her private reasons for 2 years, the analysis of the tumor volume growth was done regarding the growth rate of the tumor in the absence of intervention.

Outcomes: After 2 years of diagnosis of breast cancer, the tumor mass occupied the whole left breast with skin implanted and nipple abnormality. As this case indicated that the tumor's early growth rate was very slow. When the tumor volume reached 300 cm, its fast growth began without treatment. Later growth approached the maximum, when the tumor volume was more than 800 cm.

Lessons: The tumor growth is segmental without therapy. Early diagnosis and treatment is the key to good prognosis for every breast cancer patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000017659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824670PMC
October 2019

FAM163A, a positive regulator of ERK signaling pathway, interacts with 14-3-3β and promotes cell proliferation in squamous cell lung carcinoma.

Onco Targets Ther 2019 13;12:6393-6406. Epub 2019 Aug 13.

Department of Pathology, The First Affiliated Hospital and the College of Basic Medical Sciences of China Medical University, Shenyang, People's Republic of China.

Purpose: FAM163A, also called neuroblastoma-derived secretory protein (NDSP) or C1ORF76, was newly found on chromosome 1q25.2. Previous studies of FAM163A focused on its expression and function in neuroblastoma. However, using an online database, we found that FAM163A may predict poor prognosis in lung squamous cell carcinomas (LUSC). Therefore, the role of FAM163A plays in LUSC needs to be further clarified.

Patients And Methods: Western blots, immunofluorescence and immunohistochemistry were used to detect the effect of FAM163A on mediating cell proliferation in vitro and in vivo. Co-immunoprecipitation and immunofluorescence were utilized to evaluate the interaction and co-localization of FAM163A with 14-3-3β and ERK.

Results: In this study, our data revealed that FAM163A overexpression increased the levels of ERK and p90RSK phosphorylation and promoted the expression of cyclin D1. Incorporation with U0126 reversed the effects of FAM163A overexpression. FAM163A directly interacted with both 14-3-3β and ERK and regulated the phosphorylation of ERK by upregulating the protein level of 14-3-3β. Immunohistochemistry results also showed that FAM163A expression significantly correlated with larger tumor size (0.023), TNM staging (0.015) and regional lymph node metastasis (0.016). Kaplan-Meier survival analysis implied the mean survival time of patients with positive FAM163A expression (49.72±3.97 months) was much shorter than the patients with negative FAM163A expression (63.36±3.14 months, 0.011).

Conclusion: In summary, the present study identified a novel mechanism that FAM163A, through binding and upregulating 14-3-3β, facilitated ERK phosphorylation that led to an increase of cellular proliferation of LUSC cells. FAM163A may be a useful marker to predict poor prognosis of patients with LUSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S214731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698174PMC
August 2019

Hes3 Enhances the Malignant Phenotype of Lung Cancer through Upregulating Cyclin D1, Cyclin D3 and MMP7 Expression.

Int J Med Sci 2019 9;16(3):470-476. Epub 2019 Mar 9.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 110001, Shenyang, China.

is a basic helix-loop-helix factor gene, which was found to be involved in neural cell differentiation. Expression and clinicopathological significance of Hes3 in non-small cell lung cancer was not clear. In this study, we used immunohistochemistry to examine Hes3 expression in normal human lung and non-small cell lung cancer tissues. Hes3 expression was detected in cytoplasm and nucleus. Hes3 expression in bronchial epithelial cells and epithelial cells of submucosal glands was relatively weak and the positive rate was of 30.3% (10/33). Hes3 expression in non-small cell lung cancer tissues (51.8% (58/112)) was significantly higher than that in normal lung tissues ( < 0.05). Hes3 expression in cancer tissues was significantly associated with poor differentiation, advanced TNM stages, lymph node metastasis, and a shorter patient survival time ( < 0.05). study showed that overexpression of Hes3 in A549 cells significantly promoted cancer cell proliferation and invasion, while inhibition of Hes3 expression significantly downregulated cancer cell proliferation and invasion ( < 0.05). Western blotting showed that overexpression of Hes3 significantly upregulated expression of Cyclin D1, Cyclin D3, and MMP7 in A549 cells, while inhibition of Hes3 expression in LK2 cells significantly downregulated the expression of these molecules ( < 0.05). These results indicated that Hes3 may contribute to the malignant phenotype of non-small cell lung cancer, possibly through regulation of Cyclin D1, Cyclin D3, and MMP7, and may be a promising cancer marker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.28139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428979PMC
July 2019

Identifying UBA2 as a proliferation and cell cycle regulator in lung cancer A549 cells.

J Cell Biochem 2019 08 8;120(8):12752-12761. Epub 2019 Mar 8.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.

Ubiquitin activating enzyme 2 (UBA2) is a basic component of E1-activating enzyme in the SUMOylation system. Expression and function of UBA2 in human cancers are largely unknown. In this study we investigate UBA2 expression the function in human non-small-cell lung cancer. Immunochemistry study showed that UBA2 was overexpressed in cancer tissues (53.3%, 40 of 75) compared with normal lung tissues (14.3%, 4 of 28) (P < 0.05). Immunostaining of UBA2 was mainly detected in nucleus. Overexpression of UBA2 in cancer tissues was significantly associated with poor differentiation, large tumor size ( > 5.0 cm), higher T stages (T3 + 4), lymph node metastasis and advanced TNM stages (III + IV). In vitro study showed that UBA2 was expressed in A549, 95D, H1975, and H1299 cells. Knockdown of UBA2 in A549 cells significantly inhibited cancer cell proliferation and upregulated cancer cell apoptosis (P < 0.05). Cell cycle analysis showed that knockdown of UBA2 in A549 cell significantly increased the G1 and G2/M phase cells and reduced the S phase cells (P < 0.05). Gene expression profile after knockdown of UBA2 in A549 cells showed that the most related function was cell cycle, cell death and survival, and cellular growth and proliferation. Western blot analysis study showed that knockdown of UBA2 significantly inhibited expression of poly(ADP-ribose) polymerase 1, mini-chromosome maintenance 7 (MCM7), MCM2, MCM3 and MCM7. These results indicated that UBA2 was a critical cell cycle and proliferation regulator and may be a novel cancer marker in this malignant tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28543DOI Listing
August 2019

The function of BED finger domain of Zbed3 in regulating lung cancer cell proliferation.

J Cell Biochem 2019 08 25;120(8):12340-12347. Epub 2019 Feb 25.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

Zbed3, a BED finger domain-containing protein was found to promote cancer proliferation by regulating β-catenin expression through interacting with Axin. But whether and how BED finger domain function in regulating cancer proliferation is unknown. We constructed five mutants of Zbed3, which lacks the Axin-Zbed3 binding site, and the 43 to 52, 69 to 77, 87 to 92, and 97 to 104 sequences in BED finger domain, respectively and named them as Z-A, Z1, Z2, Z3, and Z4. Transfection of both wild-type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05), but not Z2 (P > 0.05) significantly upregulated β-catenin expression in NCI-H1299 cells. Overexpression of both wild-type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05) but not Z2 (P > 0.05) significantly promoted cancer cell proliferation and invasion. The ability of proliferation (P < 0.05) but not invasion (P < 0.05) of cancer cells transfected with Z1 and Z4 was significantly lower than that with wild-type Zbed3 and Z3. Overexpression of wild-type Zbed3 (P < 0.05) but not the mutant Z-A, which lacks the binding site with Axin and Z2 (P > 0.05) significantly upregulated the interaction of Axin and Zbed3, β-catenin expression and the activity of Wnt signaling. Both overexpression of wild-type Zbed3 and the mutant Z1 and Z4 significantly upregulated the activity of Wnt signaling and promoted cancer cell proliferation (P < 0.05) but only overexpression of wild-type Zbed3 (P < 0.05), but not the mutant Z1, and Z4 (P > 0.05), significantly upregulated the expression of proliferating cell nuclear antigen (PCNA) in NCI-H1299 cells. These results indicate that Zbed3 may promote lung cancer cell proliferation through regulating PCNA expression besides regulating β-catenin expression and BED finger domain can impact on this function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28498DOI Listing
August 2019

ZCCHC9 promotes proliferation and invasion of lung cancer through regulating the JNK pathway.

J Cell Biochem 2019 06 15;120(6):10596-10604. Epub 2019 Jan 15.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

ZCCHC9 is a type of CCHC type zinc-finger containing protein which was found to be expressed in some tissues including brain and testicles in mice. Expression and function of ZCCHC9 in human tissues including cancer was largely unknown. In this study, we investigated the expression and function of ZCCHC9 in human non-small cell lung cancer (NSCLC) and the related molecular mechanism. Immunochemistrical standing showed that ZCCHC9 was mainly located in the nucleus in bronchial epithelial cells and epithelial cells of submucosal glands (58.3% [14/24]). But in NSCLC cells ZCCHC9 was mainly located in the cytoplasm and the positive rate was 54.5% (60/110). Ectopic cytoplasmic expression of ZCCHC9 in cancer tissues was significantly associated with advanced TNM stages (III+IV), lymph node metastasis, and poor clinical outcome (P < 0.05). Overexpression of cytoplasmic ZCCHC9 using transfection of ZCCHC9 cDNA in A549 and NCI-H1299 cells significantly upregulated the proliferation and invasion of these cancer cells in vitro (P < 0.05). Western blot study showed that overexpression of cytoplasmic ZCCHC9 significantly upregulated expression of p-JNK, Cyclin D1, and MMP7 (P < 0.05). Next we used the inhibitor of JNK pathway to inhibit the activity of the JNK pathway and the results showed that co-addition of SP600125 significantly abolished the function of ZCCHC9 to promote the proliferation and invasion of cancer cells. These results indicate that cytoplasmic ZCCHC9 could promote the proliferation and invasion of NSCLC through the JNK pathway and may be a promising cancer maker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28346DOI Listing
June 2019

TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non-small cell lung cancer patients.

Mol Carcinog 2019 05 22;58(5):767-776. Epub 2019 Jan 22.

Department of Pathology, College of Basic Medical Science and the First Affiliated Hospital of China Medical University, Shenyang, China.

TIMM50 (Translocase of the inner mitochondrial membrane 50), also called TIM50, plays an essential role in mitochondrial membrane transportation. The existing literature suggests that TIMM50 may perform as an oncogenetic protein in breast cancer. However, the molecular mechanism, especially in human non-small cell lung cancer (NSCLC), is uncertain to date. In the present study, using immunohistochemistry, we found that TIMM50 expression significantly correlated with larger tumor size (P = 0.049), advanced TNM stage (P = 0.001), positive regional lymph node metastasis (P = 0.007), and poor overall survival (P = 0.001). Proliferation and invasion assay showed that TIMM50 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent Western blotting results revealed that TIMM50 enhanced the expression of Cyclin D1 and Snail, and inhibited the expression of E-cadherin. Moreover, TIMM50 facilitated the expression of phosphorylated ERK and P90RSK. Incorporation of ERK inhibitor counteracted the upregulating expression of CyclinD1, and Snail, and downregulating expression of E-cadherin expression induced by TIMM50 overexpression. In conclusion, our data indicated that TIMM50 facilitated tumor proliferation and invasion of NSCLC through enhancing phosphorylation of its downstream ERK/P90RSK signaling pathway. We speculated that TIMM50 might be a useful prognosis marker of NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.22969DOI Listing
May 2019

NDRG1 Downregulates ATF3 and Inhibits Cisplatin-Induced Cytotoxicity in Lung Cancer A549 Cells.

Int J Med Sci 2018 20;15(13):1502-1507. Epub 2018 Oct 20.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

N-myc downstream regulated gene 1 (NDRG1) plays a variety of roles in human cancers. Our previous studies showed that NDRG1 expression is elevated in non-small cell lung cancer and contributes to cancer growth. However, its function in apoptosis and chemoresistance in malignant tumors, including lung cancer, is not yet fully understood. In this study, we investigated the roles of NDRG1 in chemoresistance to cisplatin in lung cancer cells. We found that overexpression of NDRG1 significantly reduced cisplatin-induced cytotoxicity in lung cancer A549 cells, while overexpression of activating transcription factor 3 (ATF3), a stress-inducible gene found to be associated with apoptosis in some human cancers, significantly promoted cytotoxicity ( < 0.05). Further investigation showed that overexpression of NDRG1 significantly downregulated ATF3 and P53 expression in A549 cells, while overexpression of ATF3 significantly upregulated P53 expression ( < 0.05). In addition, cisplatin significantly upregulated ATF3, phospho-P53(ser46), and cleaved caspase 3 expression in lung cancer cells, but overexpression of NDRG1 in the presence of cisplatin reduced the level of these proteins elevated by cisplatin ( < 0.05). While, overexpression of ATF3 significantly promoted the cytoxicity induced by cisplatin in 1299 cells (p<0.05) (Figure 4), but overexpression of NDRG1 didn't regulate the cytoxicity induced by cisplatin (p>0.05). These results indicate that NDRG1 may contribute to cisplatin-resistance in lung cancer, possibly due to its function in the regulation of ATF3 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.28055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216061PMC
February 2019

Zbed3 promotes proliferation and invasion of lung cancer partly through regulating the function of Axin-Gsk3β complex.

J Cell Mol Med 2019 02 12;23(2):1014-1021. Epub 2018 Nov 12.

Department of Pathology, College of Basic Medical Sciences of China Medical University, Shenyang, China.

Our previous work showed that Zbed3 is overexpressed in nonsmall cell lung cancer and that down-regulation of Zbed3 inhibited β-catenin expression and cancer cell proliferation and invasiveness. Here, we investigated Zbed3's ability to promote lung cancer cell proliferation and invasion and the involvement of the Axin/TPC/glycogen synthase kinase 3β (Gsk-3β) complex to the response. Coimmunoprecipitation assays showed that wild-type Zbed3 bound to Axin but a Zbed3 mutant lacking the Axin binding site did not. In A549 and H1299 lung cancer cells, Zbed3 overexpression promoted cancer cell proliferation and invasiveness, as well as Wnt signalling and expression of downstream mediators, including β-catenin, cyclin D1 and MMP7 (P < 0.05). In contrast, the Zbed3 mutant failed to enhance β-catenin expression (P > 0.05), and its ability to promote cancer cell proliferation and invasiveness was much less than wild-type Zbed3 (P < 0.05). The ability of Zbed3 to increase β-catenin levels was abolished by Axin knockdown in A549 cells (P > 0.05). Similarly, treating the cells with a GSK-3β inhibitor abolished Zbed3's ability to increase β-catenin levels and Wnt signalling. These results indicate that Zbed3 enhances lung cancer cell proliferation and invasiveness at least in part by inhibiting Axin/adenomatous polyposis coli/GSK-3β-mediated negative regulation of β-catenin levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.14001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349170PMC
February 2019

Alveolar architectures preserved in cancer tissues may be potential pitfalls for diagnosis and histological subtyping of lung cancer: Three case reports.

Medicine (Baltimore) 2018 Sep;97(39):e12613

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

Rationale: Lung cancer is a leading cause of cancer-related deaths globally. Appropriate histopathological diagnosis and subtyping form the basis and are critical for clinical therapies.

Patient Concerns: Here, we report about 3 patients who had a nodule in the lung. Cancer cells grow in the alveolar cavity in many lung carcinomas. In all our 3 cases preserved alveolar architectures were found in tumor tissues which may lead to diagnostic pitfalls.

Diagnoses: Three patients had tumors that were diagnosed as nonsmall cell lung cancers, including large-cell carcinoma, peripheral squamous cell carcinoma, and large-cell neuroendocrine carcinoma, all of which contained structures of preserved alveolar cells that could be mistaken as malignant glandular components. The preserved alveolar cells formed acinar or duct-like structures enwrapped in the lung cancer tissues or surrounded the nests of cancer cells. Proliferative alveolar cells adjacent to cancer tissues were observed, and papillary structures and marked atypia, both of which may be mistaken as part of adenocarcinoma or carcinoma with glandular differentiation, were also observed.

Interventions: All patients underwent surgery and postoperative chemotherapy.

Outcomes: The patients had no recurrence at 5-, 8-, or 10-month follow-up after the last surgery.

Lessons: Preserved alveolar cells with different architectures may be observed in various lung cancer tissues and may be mistaken as adenocarcinoma or carcinoma with glandular differentiation. Distinct morphological and immunohistochemical features may help distinguish preserved alveolar cells from tumor components.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000012613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181608PMC
September 2018

Long period of relative quiescence in distal-type epithelioid sarcoma of the forearm with recurrence after surgery: A case report.

Medicine (Baltimore) 2018 Sep;97(36):e12276

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

Background: Epithelioid sarcoma (ES) is a rare malignant mesenchymal tumor that only accounts for 0.6% to 1.0% of all cases of sarcomas. ES with a relative quiescent state of more than 10 years is extremely rare.Here, we present a rare case of ES in the forearm of a 17-year-old girl. The patient had a congenital mass in her forearm that measured approximately 1cm; it grew rapidly starting 5 years ago. The mass was not treated until last year when she underwent the first surgery. The mass was located in the middle and lower part of the left forearm and involved the dorsal muscle group, intermuscular space, and subcutaneous tissues without clear boundaries.The patient underwent surgery, and the tumor recurred twice within 1 year postoperatively.

Methods: The tumor samples were examined via hematoxylin-eosin (HE) and immunohistochemistry staining.

Results: Histopathologically, the tumor comprised large polygonal epithelioid cells with abundant eosinophilic cytoplasm arranged in cell nests. Central necrosis and focal myxoid change could be seen in the tumor tissues. Immunostaining showed that the tumor cells were positive for CD34, CK, EMA, and vimentin but negative for CD31, S-100, and INI-1.

Conclusion: Based on these findings, the tumor was diagnosed as ES of distal form. Distal-type ES could have a long period of relative quiescence, after which it could grow rapidly and relapse multiple times over a short duration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000012276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133439PMC
September 2018

TMEM17 promotes malignant progression of breast cancer via AKT/GSK3β signaling.

Cancer Manag Res 2018 2;10:2419-2428. Epub 2018 Aug 2.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China,

Purpose: Current knowledge of TMEM17, a recently identified protein of the transmembrane (TMEM) family, is limited, especially with respect to its expression and biological functions in malignant tumors. This study analyzed TMEM17 expression in invasive breast cancer tissue and breast cell lines and its relevance to clinicopathological factors, and investigated the mechanisms underlying the biological effects of TMEM17 on breast cancer cells.

Patients And Methods: TMEM17 protein expression was determined in 20 freshly harvested specimens (tumor and paired normal tissues) by Western blotting. Immunohistochemical analysis was performed to determine the expression and subcellular localization of TMEM17 in samples from 167 patients (mean age, 49 years) diagnosed with invasive ductal carcinoma (38 with triple-negative breast cancer; 129 with non-triple-negative breast cancer) who underwent complete resection in the First Affiliated Hospital of China Medical University between 2011 and 2013. Furthermore, TMEM17 was knocked down by small interfering RNAs in breast cancer cell lines.

Results: TMEM17 was found to be significantly upregulated in breast cancer tissues compared to the corresponding normal breast tissues by Western blotting (=0.015). Immunohistochemical analysis revealed that TMEM was significantly upregulated in invasive breast cancer cells compared to adjacent normal breast duct glandular epithelial cells (10.78% vs 76.05%, <0.001), and its expression was closely related to the patient's T-stage (=0.022), advanced TNM stages (=0.007), and lymph node metastasis (=0.012). After TMEM17 knockdown or overexpression in breast cancer cell lines, TMEM17 upregulated p-AKT, p-GSK3β, active β-catenin, and Snail, and downstream target proteins c-myc and cyclin D1, and downregulated E-cadherin, resulting in increased cancer cell proliferation, invasion, and migration. These effects were reversed by the AKT inhibitor LY294002.

Conclusion: Our results indicate that TMEM17 is upregulated in breast cancer tissues and can promote malignant progression of breast cancer cells by activating the AKT/GSK3β signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S168723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080873PMC
August 2018

Intracranial immature teratoma invading the nasal cavity mimicking olfactory neuroblastoma: A case report.

Medicine (Baltimore) 2018 Jul;97(28):e11527

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Department of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, First Affiliated Hospital of China Medical University Department of Hepatobiliary and Spleenary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, China.

Rationale: Primary intracranial immature teratoma accounts for majority of congenital central nervous system germ-cell tumors, but it is extremely rare in patients older than 15 years.

Patient Concerns: A 27-year-old woman was referred to our hospital for headache, nasal congestion, and decreased olfactory sensation. Imaging showed a mass measuring approximately 5 cm × 4 cm in the right frontal lobe, which also filled the right nasal cavity. Histopathologically, the intracranial tumor tissues were composed of both mature tissues, including glands and squamous epithelial cells and immature neuroectodermal components. However, the tumor tissues in the nasal cavity were mainly immature neuroectodermal components that mimicked olfactory neuroblastoma. The cells stained positively for neuron-specific enolase, Alpha Thalassemia/Mental Retardation Syndrome X-Linked, and Oligodendrocyte transcription factor on immunostaining, proving a neuroectodermal differentiation.

Diagnoses: According to these findings, the tumor was diagnosed as a primary intracranial immature teratoma that also involved the nasal cavity after excluding the metastatic tumors.

Interventions: The patient underwent 2 surgeries. The first surgery was via the subfrontal approach, followed by a second endoscopic sinus surgery performed 22 days later.

Outcomes: The patient had no recurrence within a 6-month follow-up after the last surgery.

Lessons: When an intracranial immature teratoma involves the nasal cavity, the lesions in the nasal cavity may mimic other tumors including olfactory neuroblastoma. We suggest that thorough examination of tumor tissues and identification of variable components are critical for the appropriate diagnosis of intracranial immature teratoma, a rare tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000011527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076187PMC
July 2018

Endometriosis in the rectum accompanied by hemorrhoids leading to diagnostic pitfalls: a rare case report.

BMC Womens Health 2018 07 4;18(1):120. Epub 2018 Jul 4.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China.

Background: Hemorrhoid is a common anorectal disease. Hemorrhoids accompanied by endometriosis are unusual. As endometriosis in the rectum may mimic many other diseases, including cancer and inflammation, its diagnosis may be difficult, especially when it is combined with other diseases.

Case Presentation: Here, we present a rare case of a patient with hemorrhoids accompanied by endometriosis in the rectum. The endometriosis mass was detected by digital rectal examination and CT scan and confirmed by pathological examination. The mass was approximately 0.8 cm × 0.6 cm and located in the muscularis and submucosa of the rectum 8 cm from the anus.

Conclusions: In this case, hemorrhoid is a common disease of rectum and anal canal. However, when it is complicated by another rare disease, the rare one can be easily neglected because of the existence of the common one, especially when the two diseases have similar lesions or symptoms. We suggest that strict physical examination, such as the digital rectal examination in the current case, is critical for correct disease diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-018-0615-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030785PMC
July 2018

A rare subtype of meningioma: Case series of anaplastic meningioma and review of the literature.

Medicine (Baltimore) 2018 Jun;97(23):e11019

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Department of Hepatobiliary and Spleenary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, China.

Rationale: Anaplastic meningioma, a rare subtype of meningioma, has malignant morphological characteristics and a World Health Organization (WHO) grade of III.

Patient Concerns: In this report, we present findings from 6 cases of anaplastic meningioma.

Diagnoses: Pathological examination of the tumors, including hematoxylin and eosin staining and immunohistochemical staining, was performed. Of the six cases of anaplastic meningioma, two were recurrent tumors from original seminoma with a WHO grade of I. Histologically, three cases had carcinoma-like morphology, one case had sarcoma-like morphology, and two had two kinds of tissue structures: carcinoma-like tumor cell nests and areas with spindle tumor cells. Necrosis was detected in most cases (5/6). Ki67 index was high and varied from 20% to 70%.

Interventions: All the patients received surgery. 3 patients received adjuvant radiotherapy. 1 patient received chemotherapy.

Outcomes: 4 patients had no recurrence at follow-up of 19, 30, 46 and 54 months after the last surgery. 1 patient had recurrence 3 months after the last surgery. 1 patient died 12 days after the last surgery.

Lessons: This malignant subtype can be secondary to a WHO grade I meningioma after a long quiescent period. Necrosis was common in the tumor tissues, and Ki67 index was usually high. For patients with a history of meningioma, including benign cases, regular physical examination is important for early detection of tumor recurrence and malignant transformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000011019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999497PMC
June 2018

Hepatoblastoma with pure fetal epithelial differentiation in a 10-year-old boy: A rare case report and review of the literature.

Medicine (Baltimore) 2018 Jan;97(2):e9647

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Department of Hepatobiliary and Spleenary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, China.

Rationale: Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare.

Patient Concerns: Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins. The cut surface was multiple nodular and grey-yellow. Histologically, the small cuboidal tumor cells were arranged in trabeculae with 2-3 cell layers. The tumor cells had eosinophilic or clear cytoplasm, formed dark and light areas, and were positive for alpha-fetoprotein, CK, CK8/18, CD10, hepatocyte, and GPC3. CD34 staining revealed that the sinusoids were lined by endothelial cells in the tumor tissues. The Ki67 index was approximately 20%.

Diagnoses: Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation.

Interventions: The tumor was completely removed.

Outcomes: No recurrence was found 3 months after the operation.

Lessons: Hepatoblastoma with pure epithelial differentiation can also occur in older children. Children rarely notice and report any physical abnormality, and this may be among the primary reasons for the late diagnosis of the tumor. Annual heath checks may be beneficial in the detection of these rare tumors and improvement of patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000009647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943836PMC
January 2018

Ube2s expression is elevated in hepatocellular carcinoma and predicts poor prognosis of the patients.

Int J Clin Exp Pathol 2018 1;11(2):781-787. Epub 2018 Feb 1.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang, China.

Ube2s belongs to the ubiquitin-conjugating (E2) enzyme family of the ubiquitin system. Expression and function of Ube2s in human malignancies was largely unknown. Here we report our investigation of Ube2s expression in human non-tumor liver and hepatocellular carcinoma tissues using immunohistochemistry. Ube2s expression was detected in nuclear and cytoplasm. The positive rate of Ube2s in normal liver tissues was 19.2% (5/26). The positive rate of Ube2s expression in liver tissues with hepatocirrhosis (33.3% (6/18)) was higher than that in normal liver tissues (P<0.05). Ube2s expression in hepatocellular carcinoma (59.1% (39/66)) was higher than that in normal liver tissues and liver tissues with hepatocirrhosis (P<0.05). There were 35 cases (53.0%) showing nuclear expression, 21 cases (31.8%) showing cytoplasm expression, 17 cases (25.8%) showing both nuclear and cytoplasm expression, 18 cases (27.3%) showing only nuclear expression and 4 cases (6.1%) showing only cytoplasm expression in hepatocellular carcinoma tissues. Ube2s expression was significantly associated with higher AFP levels (>100 ng/ml), advanced TNM stages (II+III), higher ABCL stages (B+C) in hepatocellular carcinoma (P<0.05). Kaplan Meier analysis showed that Ube2s expression was significantly associated with shorter survival time of patients (<0.05). These results indicate that Ube2s may be involved in oncogenesis and development of hepatocellular carcinoma and may be a potential cancer marker and therapy target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958058PMC
February 2018

A metastasized hepatocellular carcinoma in the capsule of an undescended testis in the right inguinal area: report of a rare case.

World J Surg Oncol 2018 Jan 19;16(1):12. Epub 2018 Jan 19.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, China.

Background: Hepatocellular Carcinoma (HCC) is the most common primary carcinoma of the liver, which mainly metastasizes through the portal vein system.

Case Presentation: Here, we report an extremely rare case in which HCC metastasized to the capsule of an undescended testis in the right inguinal area of the patient. A tumor approximately 8.8 × 7.0 cm in size was found in the patient's liver during a health check-up. Initially, it was considered a metastatic tumor because the patient was found to have cryptorchidism, which had been left untreated before he presented to our hospital. The patient underwent a radical orchiectomy via inguinal approach, and the resected testis in the right inguinal region was examined via microscopy. The cancer cells were arranged in nests and showed abundant red or clear cytoplasm and marked nuclear atypia. Immunohistochemical staining showed that the tumor cells were positive for CK, CK8/18, AFP, hepatocyte, GCP3, but negative for PLAP, CD10, CD30, CD34, and vimentin.

Conclusion: According to these findings, the tumor in the inguinal region was considered a metastatic HCC arising from the liver, rather than a seminoma that had originated in the undescended testis. We suggest that during the diagnosis of malignancies, metastatic tumors should always be considered in the differential diagnosis even if the original presentation is at rare metastatic sites or concurrent with other disease(s).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-018-1319-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775560PMC
January 2018

DDEFL1 correlated with Rho GTPases activity in breast cancer.

Oncotarget 2017 Dec 26;8(68):112487-112497. Epub 2017 Oct 26.

Department of Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.

DDEFL1 is related to maintaining a limiting amount of ARF6 in GTP-loaded form by accelerating its GTP hydrolysis activity, which has been implicated in hepatocellular cancer pathogenesis and lung cancer development. We investigated DDEFL1 expression in breast cancer and paired normal breast tissues by immunohistochemistry and found that DDEFL1 expression was significantly associated with tumor size, lymph node metastasis, high content of elastosis and TNM stage but not with menopausal status or age. We detected the mRNA and protein expression of DDEFL1 in breast cancer cell lines by Western blotting and quantitative real-time PCR (qRT-PCR). DDEFL1 was obvious in MDA-MB-435s and MDA-MB-231 but very weak in ZR-75-1. Further experiments were conducted to evaluate the effect of DDEFL1 small interfering RNA (siRNA) transfection on the biological behavior of MDA-MB-231. After transfection, the effects of DDEFL1 inhibition on expression of mRNA and protein were also analyzed by Western blotting and qRT-PCR. Increased apoptosis and invasive ability, decreased cellular proliferation was found in MDA-MB-231 with successful DDEFL1 siRNA transient transfection ( < 0.05). Western blotting and qRT-PCR results showed that the DDEFL1 inhibition up-regulated Caspase-3, Apaf-1, cytochrome c, and Bax expression and down-regulated Bcl-2 expression. The DDEFL1 inhibition also down-regulated the mRNA and protein expression of Rho, CDC42 and Rac1. Our study provided a functional linkage through DDEFL1 with breast cancer biological behaviours by Rho GTPases. Possible implication of our main finding for the DDEFL1 role in breast cancer and the downstream signaling pathways for the treatment of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.22095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762527PMC
December 2017

Update on research and application of problem-based learning in medical science education.

Biochem Mol Biol Educ 2018 03 29;46(2):186-194. Epub 2017 Dec 29.

Department of Pathology, College of Basic Medical Sciences of China Medical University, Shenyang 110122, China.

Problem-based learning (PBL) is a unique form of pedagogy dedicated to developing students' self-learning and clinical practice skills. After several decades of development, although applications vary, PBL has been recognized all over the world and implemented by many medical schools. This review summarizes and updates the application and study of PBL in medical education through the literature published between 1993 and early 2017. It focuses on understanding real medical PBL courses and ways to improve PBL to achieve better learning outcomes. PBL aims to develop lifelong skills to solve practical problems rather than limiting learning to theoretical knowledge. To achieve this goal, strict and reasonable procedures need to be designed and implemented. Rigorous monitoring and timely feedback and evaluation are indispensable to constant improvements and perfecting of the process. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):186-194, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmb.21105DOI Listing
March 2018

Sellar and suprasellar granular cell tumor of the neurohypophysis: A rare case report and review of the literature.

Neuropathology 2018 Jun 21;38(3):293-299. Epub 2017 Dec 21.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

Granular cell tumors of the neurohypophysis are rare tumors with a WHO grade of I. Symptomatic tumors are even more rare. In this case, we present a 50-year-old patient with a sellar and suprasellar granular cell tumor of the neurohypophysis, who reported headaches, blurred vision and unsteady gait. CT imaging showed a sellar and suprasellar mass approximately 2.9 cm in diameter with clear boundaries. Histologically, the tumor lacked any obvious atypia and contained densely arranged polygonal tumor cells with abundant granular eosinophilic cytoplasm. Staining for Alpha-1 AntiChymotrypsin (AACT), TTF-1 and PAS was diffusely positive, and S-100 staining was focally positive in the tumor cells. CD34, CK, EMA, GFAP and HMB45 staining were negative. The Ki-67 index was < 1%. According to these findings, the tumor was diagnosed as a symptomatic granular cell tumor of the neurohypophysis. We suggest that identifying the location of the tumor with imaging is helpful for understanding the granular cell tumor of the neurohypophysis. Prompt diagnosis and treatment are critical for patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/neup.12448DOI Listing
June 2018

Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway.

Oncotarget 2017 Sep 24;8(43):75102-75113. Epub 2017 Aug 24.

Department of Pathology, Basic Medicine Science and First Hospital of China Medical University, Shenyang, China.

Lasp1 (LIM and SH3 domain protein 1) promotes tumor proliferation and invasion in multiple cancer entities including non-small cell lung cancer (NSCLC). However, the molecular mechanism is uncertain to date. In the present study, using immunohistochemistry, we found that Lasp1 expression was significantly correlated with tumor size (=0.005), advanced TNM stage (=0.042), positive regional lymph node metastasis (=0.034) and poor overall survival (<0.001). Similar results were seen in patients with squamous cell lung carcinoma (=0.003 for larger tumor size, =0.017 for advanced TNM stage, =0.003 for positive lymph node metastasis and <0.001 for poor overall survival) but not in patients with lung adenocarcinoma (>0.05). Proliferation and invasion assay showed that Lasp1 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent western blot results revealed that Lasp1 promoted the expression of Cyclin A2, CyclinB1, and Snail, and inhibited the expression of E-cadherin. Lasp1 directly interacted with FAK and facilitated the expression of phosphorylated FAK (Tyr397) and AKT (Ser473). Incorporation of both FAK inhibitor and AKT inhibitor counteracted the upregulating expression of Cyclin A2, CyclinB1, and Snail, and downregulating expression of E-cadherin expression induced by Lasp1 overexpression. Interestingly, inhibition of FAK signaling pathway attenuated the phosphorylation of AKT, but inhibition of AKT signaling pathway did not affect the phosphorylation of FAK. In conclusion, Lasp1 facilitated tumor proliferation and invasion of NSCLC through directly binding to FAK and enhancing the phosphorylation of FAK (Tyr397) and AKT (Ser473). Lasp1 may be a novel therapeutic target in the treatment of NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.20527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650404PMC
September 2017

Pathological and diagnostic implications of DCAF16 expression in human carcinomas including adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma.

Int J Clin Exp Pathol 2017 1;10(8):8585-8591. Epub 2017 Aug 1.

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University Shenyang, China.

DCAF16 is a DDB1-CUL4 associated factor. The expression pattern of DCAF16 in human carcinomas is largely unknown. Here, we investigated DCAF16 expression in a series of human normal epithelial tissues and carcinomas using immunohistochemistry. DCAF16 expression was detected mainly in the cytoplasm in epithelial tissues including thyroid follicles (3/3), epithelium of the prostate glands (2/8), epithelium of the gastric glands (1/2), bronchial epithelium (1/1), epithelium of the intestine (1/1), and hepatocellular epithelium (3/5). There were only 2 cases showing strong immunostaining. Nuclear expression of DCAF16 was detected in a few human carcinomas (0.8%, 9/83). Cytoplasmic DCAF16 expression was detected in human carcinomas including adenocarcinoma (80.0%, 52/65), squamous cell carcinoma (30.8%, 4/13), and urothelial carcinoma (100%, 5/5). The total positive rate of DCAF16 expression was 73.5% (61/83), higher than that in normal tissues (45.8%, 11/24) (P < 0.05). The positive rate of DCAF16 expression in adenocarcinoma (80.0%, 52/65) was higher than that in squamous cell carcinoma (30.8%, 4/13) (P < 0.05). Interestingly, we found that DCAF16 expression in human carcinomas was significantly associated with a higher degree of differentiation (P < 0.05). Our results suggest that DCAF16 is expressed in various human carcinomas including adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma and is not suitable to be used as a diagnostic marker for these cancers. In addition, DCAF16 expression in human carcinomas was elevated compared with that in normal epithelial tissues, suggesting its possible role in oncogenesis. However, the mechanism involved in elevation of DCAF16 expression and its function in human carcinoma needs to be further investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965455PMC
August 2017

Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients.

Mol Carcinog 2017 Dec 3;56(12):2558-2565. Epub 2017 Aug 3.

Department of Pathology, Basic Medicine Science and First Hospital of China Medical University, Shenyang, China.

Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion, and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2. In the present study, using immunohistochemistry, we found that Lasp2 expression was significantly correlated with histological type (P = 0.012), advanced TNM stage (P = 0.024), positive regional lymph node metastasis (P = 0.035), and poor overall survival (P = 0.001). Would healing assay and transwell assay results indicated that Lasp2 promoted tumor migration and invasion in NSCLC cells. Furthermore, Lasp2 facilitated Snail expression and inhibited Zo-1. The levels of phosphorylated FAK (Tyr397 and Tyr925) were obviously increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA. FAK inhibitor counteracted upregulating Snail expression and downregulating of Zo-1 expression induced by Lasp2 overexpression. Taken together, Lasp2 may facilitate tumor migration and invasion of NSCLCs through FAK-Snail/Zo-1 signaling pathway. Lasp2 may be a potential prognostic predictor of NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.22700DOI Listing
December 2017

Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway.

Tumour Biol 2017 Jun;39(6):1010428317705515

1 Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.

Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage ( p = 0.027), positive regional lymph node metastasis ( p = 0.002), and poor overall survival ( p = 0.002). Proliferation assay results showed that Noxin obviously promoted the ability of proliferation of normal breast cells. Subsequent western blot results revealed that Cyclin D1 and Cyclin E1 were upregulated by overexpressing Noxin, whereas Cyclin D1 and Cyclin E1 were downregulated after depleting Noxin. The levels of phosphorylated P38 and activating transcription factor 2 were obviously increased after overexpressing Noxin, and their expression was downregulated accordingly by transfecting Noxin-small interfering RNA. Moreover, P38 inhibitor counteracted the elevating expression of phosphorylated activating transcription factor 2, Cyclin D1, and Cyclin E1 induced by Noxin overexpression and thereby reversed the effect of Noxin overexpression on facilitating cell growth. Taken together, our studies indicated that Noxin was overexpressed in breast cancer and its positive expression was significantly correlated with advance tumor-node-metastasis stage, positive lymph node metastasis, and poor prognosis. Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1010428317705515DOI Listing
June 2017

Kctd20 promotes the development of non-small cell lung cancer through activating Fak/AKT pathway and predicts poor overall survival of patients.

Mol Carcinog 2017 09 2;56(9):2058-2065. Epub 2017 May 2.

Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.

Kctd20 (potassium channel tetramerization protein domain containing 20) is a positive regulator of Akt signaling. However, the role of Kctd20 during the course of tumorigenesis and development is unclear. Using immunohistochemistry, we demonstrated that, in non-small cell lung cancer (NSCLC) patients, Kctd20 protein expression significantly correlates with advanced TNM stage (P < 0.001), positive status for regional lymph node metastasis (P = 0.019), and poor overall survival (P = 0.013). Proliferation and invasion assays showed that Kctd20 dramatically promotes the proliferation and invasion of NSCLC cells (P = 0.007 and P < 0.001, respectively). Subsequent Western Blot and qPCR experiments revealed an upregulation of Cyclin D1 and downregulation of E-cadherin in Kctd20-overexpressing cells. After depleting Kctd20, downregulaton of Cyclin D1, and upegulation of E-cadherin was observed. After overexpressing Kctd20, the levels of phosphorylated Fak (Tyr397) and Akt (Thr308) increased, while after transfection with Kctd20-siRNA these phosporylated proteins were downregulated. Moreover, in Kctd20-overexpressing cells, treatment with an Akt inhibitor reduced expression of p-Akt and Cyclin D1, enhanced E-cadherin expression, and did not impact p-Fak levels. When Kctd20-overexpressing cells were treated with a Fak inhibitor, the same effects were seen, and the level of p-Akt was reduced. Our results suggest that Kctd20 impacts proliferation and invasion of NSCLC through enhancing Fak (Tyr397) and Akt (Thr 308) phosphorylation. Kctd20 may predict prognosis and be targeted therapeutically in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.22660DOI Listing
September 2017