Publications by authors named "Wenxiang Ji"

16 Publications

  • Page 1 of 1

Knockdown of CDK5 down-regulates PD-L1 via the ubiquitination-proteasome pathway and improves antitumor immunity in lung adenocarcinoma.

Transl Oncol 2021 Sep 12;14(9):101148. Epub 2021 Jun 12.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, PR China. Electronic address:

Although immunotherapy (anti-PD-1/PD-L1 antibodies) has been approved for clinical treatment of lung cancer, only a small proportion of patients respond to monotherapy. Hence, understanding the regulatory mechanism of PD-L1 is particularly important to identify optimal combinations. In this study, we found that inhibition of CDK5 induced by shRNA or CDK5 inhibitor leads to reduced expression of PD-L1 protein in human lung adenocarcinoma cells, while the mRNA level is not substantially altered. The PD-L1 protein degradation is mediated by E3 ligase TRIM21 via ubiquitination-proteasome pathway. Subsequently, we studied the function of CDK5/PD-L1 axis in LUAD. In vitro, the absence of CDK5 in mouse Lewis lung cancer cell (LLC) has no effect on cell proliferation. However, the attenuation of CDK5 or combined with anti-PD-L1 greatly suppresses tumor growth in LLC implanted mouse models in vivo. Disruption of CDK5 elicits a higher level of CD3, CD4 and CD8 T cells in spleens and lower PD-1 expression in CD4 and CD8 T cells. Our findings highlight a role for CDK5 in promoting antitumor immunity, which provide a potential therapeutic target for combined immunotherapy in LUAD.
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http://dx.doi.org/10.1016/j.tranon.2021.101148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215302PMC
September 2021

Distinct profile of cell-free DNA in malignant pleural effusion of non-small cell lung cancer and its impact on clinical genetic testing.

Int J Med Sci 2021 30;18(6):1510-1518. Epub 2021 Jan 30.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Cell-free DNA (cfDNA) in supernatant of pleural effusion from advanced NSCLC patients has been proved as surrogate sample detecting therapeutic targets as well as tumor mutation burden (TMB). As recently reported, cfDNA in pleural effusion supernatant is superior to plasma in TMB evaluation. It is reasonable to hypothesize that cfDNA profile in pleural effusion (PE) and plasma might be different. It remains to be elucidated why cfDNA in PE supernatant impacts on genetic analysis. Consequently, the approach dealing with cfDNA from PE supernatant might need to be different from that for plasma cfDNA in order to obtain accurate clinical genetic testing result. Pleural effusion samples from 32 patients with stage IV lung adenocarcinoma were collected. Supernatant and sediment were processed separately to extract Cell-free DNA as well as sediment DNA (PE-S). cfDNA from pleural effusion was analyzed by Agilent 2100 bioanalyzer. Libraries were prepared by 1) direct use of the total cfDNA without fragmentation step (PE-FL) or 2) use of full-length cfDNA fragmented to 150-250bp (PE-F), 3) use of cfDNA fragments enriched to ~167bp (PE-E167) as well as 4) use of cfDNA fragments larger than 500bp enriched (PE-E500). All samples were subjected to targeted next-generation sequencing (NGS) with a panel of 448 cancer-related genes as well as a panel of 10 NSCLC driver genes. cfDNA were successfully extracted from 30 MPE samples. cfDNA displayed distinct profile in supernatant of malignant pleural effusion from that of plasma cfDNA. No statistical difference in detection of hotspot variations between PE-E167 and PE-F by 448-gene or 10-gene panel. While TMB from PE-F samples was significantly higher than that from PE-E167 and PE-FL. Higher TMB from PE-F was resulted from cancer-unspecific variants with low allele frequency (0.1%-1%) which were mainly introduced by long-fragment cfDNA. Similar genetic profile was observed between paired cfDNA of PE-FL and cfDNA of PE-E167. Long-fragment cfDNA in the PE supernatant will introduce low abundant cancer unrelated variants which leads overestimation of TMB. Paired PE-FL and PE-E167 gave comparable outcomes. Direct use of the total cfDNA without fragmentation step (PE-FL) is recommended for library preparation of NGS testing in clinical practice to exclude interference from long fragments of the cfDNA.
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http://dx.doi.org/10.7150/ijms.52306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893565PMC
January 2021

Standardization of pleural effusion-based tumor mutation burden (TMB) estimation using capture-based targeted sequencing.

Ann Transl Med 2021 Jan;9(2):140

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Tumor mutation burden (TMB) has received considerable attention as a potential predictive biomarker for response to anticancer treatment with immune checkpoint inhibitors (ICIs), and has been increasingly incorporated into clinical practice. Currently, TMB is often determined with tissue biopsies using whole-exome sequencing (WES) or panel-based targeted sequencing. Meanwhile, liquid biopsies such as blood are actively investigated as alternative media, although there is currently no report of the performance of targeted sequencing in assessing TMB using pleural effusion (PE) specimens.

Methods: Thirty-two patients diagnosed with advanced non-small cell lung cancer (NSCLC) with associated PE were prospectively enrolled (NCT03546452). Cell-free DNA (cfDNA) from the supernatant of PE was subjected to both WES and capture-based targeted sequencing using various commercially-available panels.

Results: All five panels assessed in this study demonstrated a good correlation with WES-derived TMB, with correlation coefficients ranging from 0.68-0.81. Two- and three-tier classification systems built on the TMB estimates achieved respective concordance rates of 74% and 63% between classifications based on WES- and panel-derived TMB levels.

Conclusions: This study provides real-world evidence that all panels assessed in this study can be used for TMB evaluation based on PE samples. We also demonstrated that PE can serve as an alternative medium for TMB evaluation. To the best of our knowledge, this is the first study evaluating the potential of PE samples for TMB estimation, thereby providing a basis for establishing future standard protocols.
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http://dx.doi.org/10.21037/atm-20-7702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867960PMC
January 2021

Correction: FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer.

Oncogene 2020 Oct;39(42):6619-6620

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai, 200030, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41388-020-01441-6DOI Listing
October 2020

PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.

Exp Cell Res 2020 10 25;395(2):112187. Epub 2020 Jul 25.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, West Huaihai Road 241, 20030, Shanghai, China. Electronic address:

Growing evidences suggest that the overexpression of p21-activated kinase 5 (PAK5) plays an important role in various tumor progression. However, the role of PAK5 and its downstream target gene(s) in lung squamous cell carcinomas (LUSC) are waiting to be elucidated. TCGA data were utilized to evaluate the expression levels of PAK5 in LUSC. We then explored the role of PAK5 in maintaining the stem-like phenotype of lung squamous cancer cells through RT-PCR, flow cytometry, oncosphere-forming assay. In addition, co-immunoprecipitation, western blotting and immunofluorescence assays were used to determine SOX2 as a novel effector of PAK5. Xenograft models in nude mice were established to explore the roles of PAK5 in lung cancer growth. In this study, we have shown that PAK5 is overexpressed in LUSC tissues. The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo. In xenograft models, knockdown or pharmacological inhibition of PAK5 suppressed the tumor growth and metastasis of lung squamous cancer cells in vivo. Taken together, our findings suggest that the PAK5-mediated SOX2 phosphorylation promoted the cancer stem cell-like phenotype of LUSC cells. PAK5 inhibition may be a promising target in the treatment of SOX2 positive lung squamous cell cancer.
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http://dx.doi.org/10.1016/j.yexcr.2020.112187DOI Listing
October 2020

Erratum: βKlotho is identified as a target for theranostics in non-small cell lung cancer: Erratum.

Theranostics 2020;10(12):5528-5529. Epub 2020 Apr 12.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

[This corrects the article DOI: 10.7150/thno.35582.].
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http://dx.doi.org/10.7150/thno.46029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196295PMC
April 2020

Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104.

Oncogene 2020 04 28;39(17):3507-3521. Epub 2020 Feb 28.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Lung cancer occurrence and associated mortality ranks top in all countries. Despite the rapid development of targeted and immune therapies, many patients experience relapse within a few years. It is urgent to uncover the mechanisms that drive lung cancer progression and identify novel molecular targets. Our group has previously identified FGF19 as a prognostic marker and potential driver gene of lung squamous cell carcinomas (LSQ) in Chinese smoking patients. However, the underlying mechanism of how FGF19 promotes the progression of LSQ remains unclear. In this study, we characterized and confirmed that FGF19 serves as an oncogenic driver in LSQ development and progression, and reported that the amplification and high expression of FGF19 in LSQ was significantly associated with poor overall and progression-free survival. A higher serum level of FGF19 was found in lung cancer patients, which could also serve as a novel diagnostic index to screen lung cancer. Overproduction of FGF19 in LSQ cells markedly promoted cell growth, progression and metastasis, while downregulating FGF19 effectively inhibited LSQ progression in vitro and in vivo. Moreover, downregulating the receptor FGFR4 was also effective to suppress the growth and migration of LSQ cells. Since FGF19 could be induced by smoking or endoplasmic reticulum stress, to tackle the more malignant FGF19-overproducing LSQ, we reported for the first time that inhibiting mTOR pathway by using AZD2014 was effective and feasible. These findings have offered a new strategy by using anti-FGF19/FGFR4 therapy or mTOR-based therapy in FGF19-driven LSQ.
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http://dx.doi.org/10.1038/s41388-020-1227-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176586PMC
April 2020

βKlotho is identified as a target for theranostics in non-small cell lung cancer.

Theranostics 2019 12;9(25):7474-7489. Epub 2019 Oct 12.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Non-small cell lung cancer (NSCLC) remains a great challenge, calling for the identification of novel molecular targets with diagnostic/therapeutic value. Here, we sought to characterize the expression of βKlotho and its anti-tumor roles in NSCLC. The expression of βKlotho was examined in NSCLC cells and tissues by western blot, qRT-PCR and immunohistochemistry staining respectively. Biological roles of βKlotho were revealed by a series of functional and studies. Serum βKlotho concentrations of patients were measured using specific ELISA methods. Serum βKlotho concentrations of NSCLC patients were significantly lower than the control group. Moreover, βKlotho expression was negatively associated with lymph node metastasis, overall survival and progression-free survival. Overexpression of βKlotho or exogenous βKlotho administration inhibited the proliferation and migration of NSCLC cells, accompanied by induction of apoptosis, G1 to S phase arrest, and inactivation of ERK1/2, AKT and STAT3 signaling. Furthermore, βKlotho overexpression inhibited NSCLC tumor growth . βKlotho serves as a novel target for theranostics in NSCLC, which has potential clinical applications in the future.
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http://dx.doi.org/10.7150/thno.35582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831461PMC
September 2020

Reciprocal regulatory mechanism between miR-214-3p and FGFR1 in FGFR1-amplified lung cancer.

Oncogenesis 2019 Sep 6;8(9):50. Epub 2019 Sep 6.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, 20030, Shanghai, China.

MicroRNA (miRNA) and fibroblast growth factor receptor 1 (FGFR1) dysregulation are considered to play an important role in tumor proliferation, invasion, and metastasis. However, the regulatory mechanism between miRNAs and FGFR1 in lung cancer remains unclear and extremely critical. miR-214-3p was sharply decreased and showed a significantly negative correlation with FGFR1 in lung cancer patients (n = 30). Luciferase reporter assay confirmed that miR-214-3p could downregulate FGFR1 by directly targeting 3'-untranslated region (UTR). miR-214-3p inhibited the processes of epithelial-mesenchymal transition and Wnt/MAPK/AKT (Wnt/mitogen-activated protein kinase/AKT) signaling pathway by targeting FGFR1. Moreover, miR-214-3p not only established a negative feedback regulation loop with FGFR1 through ERK (extracellular signal-regulated kinase) but also developed a synergism with FGFR1 inhibitor AZD4547. In conclusion, our study demonstrated the regulatory mechanism between miR-214-3p and FGFR1 in lung cancer. miR-214-3p acts as a vital target in FGFR1-amplified lung cancer by forming a miR-214-3p-FGFR1-Wnt/MAPK/AKT signaling pathway network. Co-targeting miR-214-3p and FGFR1 could provide greater benefits to patients with FGFR1-amplified lung cancer.
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http://dx.doi.org/10.1038/s41389-019-0151-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731303PMC
September 2019

Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma.

Exp Cell Res 2019 06 10;379(2):203-213. Epub 2019 Apr 10.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai, 200030, China. Electronic address:

Tumor-derived exosomes contain informative microRNAs involved in carcinogenesis, cell migration, invasion and epithelial-mesenchymal transition (EMT), eventually contributing to metastasis of cancers. This study aims to clarify which and how exosomal miRNA affects tumor carcinogenesis and metastasis. Among them, miR-499a-5p was upregulated in both highly metastatic lung cancer cell line and their exosomes. MiR-499a-5p overexpression promoted cell proliferation, migration and EMT, while miR-499a-5p knockdown suppressed these processes in vitro. Inhibition of miR-499a-5p by antagomirs administration restrained tumor growth in vivo. Consequently, miR499a-sufficient exosomes, derived from highly metastatic cell line, enhanced cell proliferation, migration and EMT via mTOR pathway, and the effect could be inhibited by miR-499a-5p inhibitor. The study reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-499a-5p, and sheds a new insight on a novel molecular mechanism which modulates metastasis.
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http://dx.doi.org/10.1016/j.yexcr.2019.03.035DOI Listing
June 2019

FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer.

Oncogene 2018 09 1;37(39):5340-5354. Epub 2018 Jun 1.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai, 200030, China.

Epithelial-mesenchymal transition (EMT) is an important process for cancer metastasis, drug resistance, and cancer stem cells. Activation of fibroblast growth factor receptor 1 (FGFR1) was found to promote EMT and metastasis in prostate and breast cancers, but the effects and mechanisms in lung cancer was unclear. In this study, we aimed to explore whether and how activation of FGFR1 promotes EMT and metastasis in FGFR1-amplified lung cancer. We show that activation of FGFR1 by its ligand fibroblast growth factor 2 (FGF2) promoted proliferation, EMT, migration, and invasion in FGFR1-amplified lung cancer cell lines H1581 and DMS114, whereas inhibition of FGFR1 suppressed these processes. FGFR1 activation upregulated expression of Sry-related HMG box 2 (SOX2) by downstream phosphorylated ERK1/2; moreover, the upregulation of SOX2 by autophosphorylation variant ERK2_R67S plasmid transfection was not suppressed by FGFR1 inhibitor AZD4547 or MEK/ERK inhibitor AZD6244 in vitro. And SOX2 expression was also significantly upregulated in ERK2_R67S lentivirus-transfected stable cell lines in vivo. Overexpression of SOX2 promoted cell proliferation, EMT, migration, and invasion. Importantly, activation of FGFR1 could not promote these processes in SOX2-silenced stable cell lines. In orthotopic and subcutaneous lung cancer xenograft models, inhibition of FGFR1 suppressed tumor growth, SOX2 expression, EMT, and metastasis in vivo; however, these processes caused by SOX2-overexpressing stable cell lines were not suppressed by FGFR1 inhibition. Higher expression of FGFR1 and SOX2 were positively correlated, and both were associated with shorter survival in lung cancer patients. In conclusion, our findings reveal that activation of FGFR1 promotes cell proliferation, EMT, and metastasis by the newly defined FGFR1-ERK1/2-SOX2 axis in FGFR1-amplified lung cancer.
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http://dx.doi.org/10.1038/s41388-018-0311-3DOI Listing
September 2018

Corrigendum to "The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer" [Canc. Lett. 423 (2018) 36-46].

Cancer Lett 2018 Sep 10;431:244. Epub 2018 May 10.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.canlet.2018.04.014DOI Listing
September 2018

The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer.

Cancer Lett 2018 06 13;423:36-46. Epub 2018 Feb 13.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China. Electronic address:

The Hippo pathway plays a critical role in organ size control, tissue homeostasis and tumor genesis through its key transcription regulator Yes-associated protein1 (YAP1), but the mechanism underlying its role in lung cancer is unclear. We hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our data confirms that expression levels of YAP1 are positively associated with those of FGFR1 in clinical lung carcinoma samples as measured by real-time PCR, western blot, and immunohistochemistry (IHC) staining. Mechanistically, YAP1 up-regulates FGFR1 expression at the level of promoter through the TEAD binding site while bFGF/FGFR1 induces YAP1 expression via large tumor suppressors 1(LATS1). In addition, the absence of YAP1 abolishes self-renewal ability in lung cancer. Furthermore, an orthotropic mouse model highlights the function of YAP1 in the initiation and metastasis of lung cancer. Verteporfin, a YAP1 inhibitor, effectively inhibits both YAP1 and FGFR1 expression in lung cancer. Thus, we conclude that YAP1 is a potential therapeutic target for lung cancer. Combined targeting of YAP1 and FGFR1 may provide benefits to patients with FGFR1-amplified lung cancer.
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http://dx.doi.org/10.1016/j.canlet.2018.02.015DOI Listing
June 2018

A novel paclitaxel-loaded poly(d,l-lactide-co-glycolide)-Tween 80 copolymer nanoparticle overcoming multidrug resistance for lung cancer treatment.

Int J Nanomedicine 2016 25;11:2119-31. Epub 2016 May 25.

Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Drug resistance has become a main obstacle for the effective treatment of lung cancer. To address this problem, a novel biocompatible nanoscale package, poly(d,l-lactide-co-glycolide)-Tween 80, was designed and synthesized to overcome paclitaxel (PTX) resistance in a PTX-resistant human lung cancer cell line. The poly(d,l-lactide-co-glycolide) (PLGA)-Tween 80 nanoparticles (NPs) could efficiently load PTX and release the drug gradually. There was an increased level of uptake of PLGA-Tween 80 in PTX-resistant lung cancer cell line A549/T, which achieved a significantly higher level of cytotoxicity than both PLGA NP formulation and Taxol(®). The in vivo antitumor efficacy also showed that PLGA-Tween 80 NP was more effective than Taxol(®), indicating that PLGA-Tween 80 copolymer was a promising carrier for PTX in resistant lung cancer.
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http://dx.doi.org/10.2147/IJN.S92271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887048PMC
March 2017

Identification of FGF19 as a prognostic marker and potential driver gene of lung squamous cell carcinomas in Chinese smoking patients.

Oncotarget 2016 Apr;7(14):18394-402

Shanghai Lung Cancer Center, Lung Cancer Research Laboratory, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, China.

Comprehensive genomic characterizations of lung squamous cell carcinoma (LSCC) have been performed, but the differences between smokers (S-LSCC) and never smokers (NS-LSCC) are not clear, as NS-LSCC could be considered as a different disease from S-LSCC. In this study we delineated genomic alterations in a cohort of 21 NS-LSCC and 16 S-LSCC patients, and identified common gene mutations and amplifications as previously reported. Inclusion of more NS-LSCC patients enabled us to identify unreported S-LSCC- or NS-LSCC-specific alterations. Importantly, an amplification region containing FGF19, FGF3, FGF4 and CCND1 was found five-times more frequent in S-LSCC than in NS-LSCC. Amplification of FGF19 was validated in independent LSCC samples. Furthermore, FGF19 stimulated LSCC cell growth in vitro. These data implicate FGF19 as a potential driver gene in LSCC with clinic characteristics as smoking.
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http://dx.doi.org/10.18632/oncotarget.7817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951296PMC
April 2016

FGFR1 promotes the stem cell-like phenotype of FGFR1-amplified non-small cell lung cancer cells through the Hedgehog pathway.

Oncotarget 2016 Mar;7(12):15118-34

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

Cancer stem cell-like phenotype is critical for tumor formation and treatment resistance. FGFR1 is found to be amplified in non-small cell lung cancer, particularly in the lung squamous cell cancer (LSCC). Whether FGFR1 contributes to the maintenance of stem cell-like phenotype of FGFR1-amplified lung cancer cells remains elusive. In this study, treatment with FGFR1 inhibitor AZD4547 suppressed the growth of tumor spheres and reduced ALDH positive proportion in FGFR1-amplified lung cancer cells in vitro, as well as inhibited the growth of oncospheres and parental cells in xenograft models. Knockdown of FGFR1 recaptured the similar effect as AZD4547 in vitro. Furthermore, activation of FGFR1 and subsequently its downstream ERK signaling enhanced the expression and transcriptional activity of GLI2, which could be blocked by FGFR1 inhibitor/silencing or ERK inhibitor. Knockdown of GLI2 directly inhibited the stem-like phenotype of FGFR1-amilified cells, whereas overexpression of GLI2 sufficiently rescued the phenotype caused by FGFR1 knockdown. Notably we also identified a correlation between FGFR1 and GLI2 expressions from clinical data, as well as an inverse relationship with progression free survival (PFS). Together our study suggests that the FGFR1/GLI2 axis promotes the lung cancer stem cell-like phenotype. These results support a rational strategy of combination of FGFR1 and GLI inhibitors for treatment of FGFR1-amplified lung cancers, especially LSCC.
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http://dx.doi.org/10.18632/oncotarget.7701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924774PMC
March 2016
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