CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells

Yuan, Yeqing1; Sheng, Zhengzuo2; Liu, Zhenhua3; Zhang, Xiaowei4; Xiao, Yunbei5; Xie, Jing1; Zhang, Yixiang1; Xu, Tao4

2020

10.7150/jca.42314

Journal of Cancer   影响因子和分区

1837-9664

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.

CMTM5 tumor suppressor gene castration-resistant prostate cancer EGFR tyrosine kinase inhibitors Gefitinib

SCI

英语

第一 ; 通讯

Scientific research cultivation project of Shenzhen People's Hospital[SYKYPY201907]

Oncology

Oncology

WOS:000526089900008

IVYSPRING INT PUBL

Web of Science

1.Southern Univ Sci & Technol, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Urol,Jinan Univ,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
2.Capital Med Univ, Fu Xing Hosp, Dept Thorac Surg, Beijing 100038, Peoples R China
3.Beijing Jishuitan Hosp, Dept Urol, Beijing 100096, Peoples R China
4.Peking Univ, Dept Urol, Peoples Hosp, Beijing 100044, Peoples R China
5.Wenzhou Med Univ, Dept Urol, Affiliated Hosp 1, Wenzhou 325000, Peoples R China

Yuan, Yeqing,Sheng, Zhengzuo,Liu, Zhenhua,et al. CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells[J]. Journal of Cancer,2020,11(13):3762-3770.

Yuan, Yeqing.,Sheng, Zhengzuo.,Liu, Zhenhua.,Zhang, Xiaowei.,Xiao, Yunbei.,...&Xu, Tao.(2020).CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells.Journal of Cancer,11(13),3762-3770.

Yuan, Yeqing,et al."CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells".Journal of Cancer 11.13(2020):3762-3770.