CMTM5 is reduced in prostate cancer and inhibits cancer cell growth in vitro and in vivo
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A novel tumor suppressor CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) is reduced or undetectable in many kinds of cancers and inhibits tumor cells’ malignant features. To explore its role in prostate cancer (PCa), we detected its expression patterns in prostate tissues and PCa cells, and determined its anti-proliferation functions in PCa cells in vitro and in vivo.
The expression of CMTM5 in prostate tissue microarray, specimens and cell lines was evaluated by immunohistochemistry and Western blot, respectively. After being transfected with CMTM5 adenovirus or vector, the proliferation and migration of DU145 cells were detected by MTT assay and transwell assay, respectively. Furthermore, the effects of CMTM5 on tumor growth were performed in nude mice xenograft in vivo.
We found CMTM5 was reduced in PCa tissues and cells compared with BPH tissues, and its expression in PCa tissues was related to the Gleason score. Moreover, after being transfected with adenovirus, ectopic expression of CMTM5-v1 in DU145 cells led to significant inhibition of cell proliferation and migration compared with the control, which may be attributed to decreased Akt activity. Finally, restoration of CMTM5 significantly suppressed tumor growth in vivo.
These results indicate that CMTM5 is down-regulated in PCa and exhibit tumor suppressor activities in androgen-independent PCa cells. Loss of CMTM5 protein may be contributed to the development of PCa and it is a potential therapeutic target for castration-resistant prostate cancer.
KeywordsCMTM5 Prostate cancer TM4SF Tumor suppressor gene Gene therapy
This work was supported by the National Natural Science Foundation of China (NSFC) 81072099. We thank Drs. Wenling Han for her generous offer of adenovirus vector and antibody. We also thank Weidong Yu, Yidong Niu and Henan Li for some technical support, and Jianqiang Dong and the Department of Pathology, Peking University People’s Hospital for support for IHC and staining evaluation.
Conflict of interest
The authors declare no conflict of interest.
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