| Title | BRM/SMARCA2 promotes the proliferation and chemoresistance of pancreatic cancer cells by targeting JAK2/STAT3 signaling |
| Authors | Zhang, Zhengkui Wang, Feng Du, Chong Guo, Huahu Ma, Ling Liu, Xiaoran Kornmann, Marko Tian, Xiaodong Yang, Yinmo |
| Affiliation | Peking Univ, Hosp 1, Dept Gen Surg, 8th Xishiku St, Beijing 100034, Peoples R China. Univ Ulm, Clin Gen Visceral & Transplantat Surg, D-89081 Ulm, Germany. Capital Med Univ, Beijing Shijitan Hosp, Peking Univ, Dept Surg Oncol,Sch Clin Med 9, Beijing 100038, Peoples R China. Peking Univ Canc Hosp & Inst, Dept Breast Oncol, Beijing 100142, Peoples R China. |
| Keywords | BRM/SMARCA2 Pancreatic cancer Chemoresistance STAT3 phosphorylation JAK2/STAT3 signaling SWI/SNF COMPLEXES BAF COMPLEXES BRM EXPRESSION STAT3 TRANSCRIPTION PATHWAYS GENES BRG1 ACTIVATION |
| Issue Date | 2017 |
| Publisher | CANCER LETTERS |
| Citation | CANCER LETTERS.2017,402,213-224. |
| Abstract | Background: BRM is one of two evolutionarily conserved catalytic ATPase subunits of SWI/SNF complexes and plays important role in cell proliferation, linage specification and development, cell adhesion, cytokine responses and DNA repair. BRM is often inactivated in various types of cancer indicating its indispensable roles in oncogenesis but the mechanisms remain poorly understood. Methods: BRM expression in clinical pancreatic cancer samples was examined by immunohistochemistry and the correlation with patient survival was analyzed. shRNAs targeting BRM were used to establish stable BRM knockdown BxPC-3 and T3M4 cell lines. Cell viability was assessed by CCK-8 assay. Cell proliferation was measured by EdU incorporation assay, colony formation assay and Ki67 staining. Cell cycle and apoptosis were examined by flow cytometry. Growth and chemosensitivity of xenografts initiating from BRM-deficient cells were evaluated, and in situ apoptosis was detected by TUNEL assay. The status of JAK-STAT3 signaling was examined by real-time PCR and Western blot analysis. Results: High BRM expression was correlated with worse survival of pancreatic cancer patients. BRM shRNA reduced the proliferation and increased the sensitivity of pancreatic cancer cells to gemcitabine in vivo and in vitro, and these effects are associated with the inhibition of STAT3 phosphorylation and reduced transcription of STAT3 target genes. Conclusion: We reveal a novel mechanism by which BRM could activate JAK2/STAT3 pathway to promote pancreatic cancer growth and chemoresistance. These findings may offer potential therapeutic targets for pancreatic cancer patients with excessive BRM expression. (C) 2017 Elsevier B.V. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/471372 |
| ISSN | 0304-3835 |
| DOI | 10.1016/j.canlet.2017.05.006 |
| Indexed | SCI(E) |
| Appears in Collections: | 第一医院 北京世纪坛医院 北京肿瘤医院 |
