ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2020; 11(13):3762-3770. doi:10.7150/jca.42314 This issue Cite
Research Paper
CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells
1. Department of Urology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China
2. Department of Thoracic Surgery, Fu Xing Hospital, Capital Medical University, Beijing, 100038, China
3. Department of Urology, Beijing Jishuitan Hospital, Beijing, 100096, China
4. Department of Urology, Peking University People's Hospital, Beijing, 100044, China
5. Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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-v1can 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.
Keywords: CMTM5, tumor suppressor gene, castration-resistant prostate cancer, EGFR, tyrosine kinase inhibitors, Gefitinib
Citation styles
