Publications by authors named "Delu Gan"

7 Publications

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[Progranulin (PGRN) promotes invasion and migration of mouse breast cancer 4T1 cells by promoting epithelial-mesenchymal transition of cancer cells and activating ERK1/2 pathway].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Feb;37(2):125-131

Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effect of progranulin (PGRN) on the invasion and migration of mouse breast cancer 4T1 cells and its mechanism. Methods After treated with PGRN (1 μg/mL) for 24 hours, the invasion ability of breast cancer 4T1 cells was detected by Transwell invasion assay, the migration ability was detected by scratch test, and the epithelial cadherin (E-cadherin), vimentin mRNA expression was detected by real-time fluorescent quantitative PCR. Western blot assay was used to detect the expression of E-cadherin, vimentin, extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2). After treated with 1 μg/mL PGRN and ERK1/2 signaling pathway inhibitor U0126 (10 μmol/L) simultaneously, the migration and invasion ability of 4T1 cells and the changes in the expression of E-cadherin, vimentin and p-ERK proteins were detected again. Results After treated with PGRN, the migration and invasion capabilities of breast cancer 4T1 cells were significantly enhanced; E-cadherin expression decreased; vimentin and p-ERK1/2 expression increased. After treated with ERK1/2 signaling pathway inhibitor, the ability of PGRN to promote breast cancer 4T1 cell migration, invasion and epithelial-mesenchymal transition (EMT) was significantly inhibited. Conclusion PGRN can promote the migration and invasion of breast cancer 4T1 cells by promoting EMT and activating the ERK1/2 pathway.
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February 2021

PGRN TAMs-derived exosomes inhibit breast cancer cell invasion and migration and its mechanism exploration.

Life Sci 2021 Jan 9;264:118687. Epub 2020 Nov 9.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address:

Breast cancer is one of the most malignant diseases world-wide and ranks the first among female cancers. Progranulin (PGRN) plays a carcinogenic role in breast cancer, but its mechanisms are not clear. In addition, there are few reports on the relationship between PGRN and tumor-associated macrophages (TAMs).

Aims: To investigate the effects of exosomes derived from PGRN TAMs on invasion and migration of breast cancer cells.

Main Methods: Mouse breast cancer xenograft model was constructed to explore the effect of PGRN tumor environment (TME) on breast cancer. Flow cytometry was used to compare TAMs of wild type (WT) and PGRN tumor tissue. Transwell assay, wound healing assay and western blot were used to explore the effect of WT and PGRN TAMs and their exosomes on invasion, migration and epithelial-mesenchymal transition (EMT) of breast cancer cells. MicroRNA (miRNA) assay was used to find out the differentially expressed miRNA of negative control (NC) and siPGRN-TAMs exosomes. Quantitative PCR and luciferase report assay were used to explore the target gene.

Key Findings: The lung metastasis of breast cancer of PGRN mice was inhibited. PGRN TAMs inhibited invasion, migration and EMT of breast cancer cells through their exosomes. MiR-5100 of PGRN TAMs-derived exosomes was up-regulated, which might regulate expression of CXCL12, thereby inhibiting the CXCL12/CXCR4 axis, and ultimately inhibiting the invasion, migration and EMT of breast cancer cells.

Significance: Our study elucidates a new molecular mechanism of lung metastasis of breast cancer, so it may contribute to efficient prevention and therapeutic strategies.
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http://dx.doi.org/10.1016/j.lfs.2020.118687DOI Listing
January 2021

Nucleus-located PDK1 regulates growth, invasion and migration of breast cancer cells.

Life Sci 2020 Jul 26;253:117722. Epub 2020 Apr 26.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address:

Aims: It is well known that pyruvate dehydrogenase kinase 1 (PDK1) is highly expressed in breast cancer (BC) tissues and promotes tumor growth, but the underlying mechanisms of this process are unclear. Here, we investigated the effects of nuclear PDK1 on growth, migration and invasion in human BC cells.

Main Methods: The sub-cellular localization of PDK1 in BC cells was performed with subcellular fractionation followed by Western blot and immunofluorescence. The localization of PDK1 in breast normal tissue and breast duct carcinoma was detected by Immunohistochemistry. Then the protein-protein interaction between PDK1 and Importin β was verified by co-immunoprecipitation assay. Finally, the effects of nuclear PDK1 on cell proliferation, apoptosis, migration and invasion of BC cells were assessed.

Key Findings: In addition to its well-known sub-cellular localization, PDK1 was present in the nucleus of BC cells, and EGF treatment increased nucleus distribution of PDK1. Moreover, the level of nuclear PDK1 accumulation facilitated the growth of BC cells. We also found that the entry of PDK1 into nucleus mainly relied on the nuclear localization signal (NLS), and NLS mutation inhibited the entry of PDK1 into nucleus; as a result, the migration and invasion abilities of BC cells were impaired, and the number of apoptotic cells was significantly increased.

Significance: Our findings provided a new supplement to the sub-cellular localization of PDK1 in BC cells and uncovered the function of nuclear PDK1 in facilitating BC cells growth, migration and invasion.
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http://dx.doi.org/10.1016/j.lfs.2020.117722DOI Listing
July 2020

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells.

Cell Death Dis 2020 04 27;11(4):293. Epub 2020 Apr 27.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.
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http://dx.doi.org/10.1038/s41419-020-2496-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184624PMC
April 2020

[Molecular mechanism of macrophages derived from PGRN gene knockout mice inhibit invasion and migration of breast cancer cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Sep;35(9):769-775

Ministry-of-Education Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To explore the functions and mechanisms of macrophages derived from PGRN gene knockout (PGRN ) C57BL/6 mice in the invasion and migration of breast cancer cells. Methods Breast cancer cells were cultured in conditioned medium of macrophages derived from WT and PGRN mice. Transwell assay and scratch assay were used to detect the invasion and migration ability of cancer cells. Western blot analysis was used to detect the expression of E-cadherin and N-cadherin in cancer cells. Cytokine array, real-time quantitative PCR and ELISA were performed to investigate the differences of cytokines secreted by macrophages derived from WT and PGRN mice. Breast cancer cells were treated by the differentially expressed cytokine interleukin-6 (IL-6), and then the above methods were used to investigate its effect on cancer cells. Western blot analysis was used to verify the roles of NF-κB and JAK/STAT3 signaling pathways. Results The macrophages derived from PGRN mice blocked NF-κB signaling pathway, reduced IL-6 secretion, and inhibited the invasion and migration of breast cancer cells. IL-6 activated JAK/STAT3 signaling pathway to promote the invasion and migration of breast cancer cells. Conclusion The macrophages derived from PGRN mice can block the NF-κB and JAK/STAT3 signaling pathways, down-regulate IL-6 expression, and inhibit the invasion and migration of breast cancer cells.
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September 2019

Fiber optic surface plasmon resonance biosensor for detection of PDGF-BB in serum based on self-assembled aptamer and antifouling peptide monolayer.

Biosens Bioelectron 2019 Sep 25;140:111350. Epub 2019 May 25.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:

Herein, a home-build fiber optic surface plasmon resonance (FO-SPR) biosensing platform has been developed for highly sensitive detection of platelet-derived growth factor (PDGF-BB) based aptamer-functionalized AuNPs for signal enhancement. In this biosensor, the PDGF-BB aptamer was used to specifically capture PDGF-BB, and the antifouling peptide demonstrated great ability for resisting non-specific adsorption. After a sandwich reaction, the aptamer, PDGF-BB and aptamer-functionalized AuNPs complexes were formed on the fiber optic (FO) probe surface to significantly amplify FO-SPR signal. This method exhibited a broad detection range from 1 to 1000 pM of PDGF-BB and a low detection limit of 0.35 pM. Moreover, this biosensor was successfully applied to the detection of PDGF-BB in 10% human serum samples without suffering from serious interference owing to the excellent antifouling property of the peptide. Thus, this developed FO-SPR biosensor could be a potential alternative device for proteins determination, even as a point-of-care diagnostic tool (POCT) in clinical application.
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http://dx.doi.org/10.1016/j.bios.2019.111350DOI Listing
September 2019

The miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in breast cancer cells.

Oncogene 2019 07 9;38(28):5551-5565. Epub 2019 Apr 9.

Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, 400016, Chongqing, China.

Tamoxifen resistance is one of the major challenges for its medical uses in estrogen receptor (ER)-positive breast cancer. Aerobic glycolysis, an anomalous characteristic of glucose metabolism in cancer cells, has been shown to associate with the resistance to chemotherapeutic agents. It remains, however, largely unclear whether and how tamoxifen resistance contributes to aerobic glycolysis in breast cancer. Here, we report that tamoxifen resistance is associated with enhanced glycolysis in ER-positive breast cancer cells. We demonstrate that EREG, an agonist of EGFR, has an important role in enhancing glycolysis via activating EGFR signaling and its downstream glycolytic genes in tamoxifen-resistant breast cancer cells. We further show that EREG is a direct target of miR-186-3p and that downregulation of miR-186-3p by tamoxifen results in EREG upregulation in tamoxifen-resistant breast cancer cells. Importantly, systemic delivery of cholesterol-modified agomiR-186-3p to mice bearing tamoxifen-resistant breast tumors effectively attenuates both tumor growth and [F]-fluoro-deoxyglucose ([F]-FDG) uptake. Together, our results reveal a novel molecular mechanism of resistance to hormone therapies in which the miR-186-3p/EREG axis orchestrates tamoxifen resistance and aerobic glycolysis in ER-positive breast cancer, suggesting targeting miR-186-3p as a promising strategy for therapeutic intervention in endocrine-resistant breast tumors.
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http://dx.doi.org/10.1038/s41388-019-0817-3DOI Listing
July 2019