CMTM4 inhibits cell proliferation and migration via AKT, ERK1/2,and STAT3 pathway in colorectal cancer  

作　　者：Hui Xue Ting Li Pingzhang Wang Xiaoning Mo Hejun Zhang Shigang Ding Dalong Ma Wenping Lv Jing Zhang Wenling Han 

机构地区：[1]Peking University Center for Human Disease Genomics,Department of Immunology,Key Laboratory of Medical Immunology,Ministry of Health,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China [2]Department of Gastroenterology,Peking University Third Hospital,Beijing 100191,China [3]Department of Hepatobiliary Surgery,First Medical Center,Chinese PLA General Hospital,Beijing 100853,China

出　　处：《Acta Biochimica et Biophysica Sinica》2019年第9期915-924,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(Nos.81870386,30772493,and 81170429);the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2018PT31039).

摘　　要：CMTM4(CKLF-like MARVEL transmembrane domain containing 4),a potential tumor suppressor gene,is involved in several types of malignancies.It has been reported to be downregulated and exhibit anti-tumorigenic activities by regulating cell growth and cell cycle in clear cell renal cell carcinoma.It has also been identified as a tumor suppressor in hepatocellular carcinoma(HCC),and its negative expression is a risk factor for poor prognosis of HCC patients.In the present study,an integrated bioinformatics analysis based on The Cancer Genome Atlas(TCGA)database showed that CMTM4 was frequently reduced in colorectal cancer(CRC)and high expression of CMTM4 was associated with increased overall survival rates.Based on these findings,we adopted gain-of-function and lost-of-function strategies using SW480 and HT29 CRC cell lines which have relatively low and high endogenous CMTM4 levels,respectively.We observed impeded cell proliferation and migration upon overexpression of CMTM4 in SW480 cells,and the opposite effects were observed upon knockdown of CMTM4 in HT-29 cells.Cell signaling pathways essential for CRC progression were then examined,and the phosphorylation levels of AKT,ERK1/2,and STAT3 were found to be decreased by CMTM4 overexpression in SW480 cells and elevated by CMTM4 silencing in HT29 cells.Their inhibitors were used to validate that the three signaling pathways contributed to the inhibitory effects of CMTM4 on CRC cells.Taken together,our results suggest that CMTM4 plays a tumor suppressive role in CRC.

关 键 词：CMTM4 CRC proliferation MIGRATION 

分 类 号：R73[医药卫生—肿瘤]