| Title | CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells |
| Authors | Yuan, Yeqing Sheng, Zhengzuo Liu, Zhenhua Zhang, Xiaowei Xiao, Yunbei Xie, Jing Zhang, Yixiang Xu, Tao |
| Affiliation | Southern Univ Sci & Technol, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Urol,Jinan Univ,Affiliated Hosp 1, Shenzhen 518020, Peoples R China Capital Med Univ, Fu Xing Hosp, Dept Thorac Surg, Beijing 100038, Peoples R China Beijing Jishuitan Hosp, Dept Urol, Beijing 100096, Peoples R China Peking Univ, Dept Urol, Peoples Hosp, Beijing 100044, Peoples R China Wenzhou Med Univ, Dept Urol, Affiliated Hosp 1, Wenzhou 325000, Peoples R China |
| Keywords | GROWTH-FACTOR RECEPTOR ANDROGEN-INDEPENDENCE EXPRESSION GENE GEFITINIB PROGRESSION ACTIVATION INVASION PROTEIN OVEREXPRESSION |
| Issue Date | 2020 |
| Publisher | JOURNAL OF CANCER |
| Abstract | Anomalous epidermal growth factor receptor (EGFR) signaling plays an important role in the progression of prostate cancer (PCa) and the transformation to castration-resistant PCa (CRPC). A novel tumor suppressor CKLF-like MARVEL transmembrane domain-containing member 5(CMTM5) has a MARVEL domain and may regulate transmembrane signaling. Thus, we postulated that CMTM5 could regulate EGFR and its downstream molecules to affect the biological behaviors of PCa cells. In this study, we found that CMTM5 was expressed in benign prostatic hyperplasia (BPH) tissues but was undetectable in PCa cells. However, the EGFR was upregulated in PCa cells, especially in two metastatic CRPC cell lines, PC3 and DU145. Furthermore, ectopic expression of CMTM5-v1 suppressed cell proliferation and migration and p-EGFR levels. Further investigation revealed that restoration of CMTM5-v1 inhibited not only EGF-mediated proliferation but also chemotactic migration by EGF in PC3 and DU145 cells. Moreover, mechanistic studies showed that CMTM5-v1 attenuated EGF-induced receptor signaling by repressing EGFR and Akt phosphorylation in PCa cells, which were essential for malignant features. Finally, CMTM5-v1 can promote the sensitivity of PC3 cells to Gefetinib, a tyrosine kinase inhibitor (TKI) targeting the EGFR. These observations indicate that CMTM5-v1 suppressed PCa cells through EGFR signaling. The loss of CMTM5 may participate in the progression of PCa resulting from deregulated EGFR, and CMTM5 might be associated with the efficacy of TKIs in terms of their potent inhibition of EGFR and human epidermal growth factor-2 (HER2) activation. |
| URI | http://hdl.handle.net/20.500.11897/588001 |
| ISSN | 1837-9664 |
| DOI | 10.7150/jca.42314 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
