CMTM5 is downregulated and suppresses tumour growth in hepatocellular carcinoma through regulating PI3K-AKT signalling

Gang Xu,Chengxue Dang

doi:10.1186/s12935-017-0485-8

Abstract

BackgroundHuman chemokine like factor (CKLF)-like MAL and related proteins for vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been shown to involved and may function as a tumour suppressor in tumorigenesis. The current study aimed to investigate the expression and function of CMTM5 in human hepatocellular carcinoma (HCC).MethodsCMTM5 expression was examined by immunohistochemistry, and its clinical significance was analysed in 76 HCC specimens. The role and molecular mechanisms of CMTM5 in cell proliferation, apoptosis and invasion were examined in vitro and in vivo.ResultsCMTM5 expression was significantly downregulated in HCC tissues as well as cell lines. The expression of CMTM5 was absent in 77.6% of HCC tissues compared with 3.9% in normal liver tissues. Low CMTM5 expression was significantly correlated with poor overall survival in patients with HCC (P = 0.009). Restoring CMTM5 expression in Huh7 cells significantly inhibited cell growth, promoted cell apoptosis, and reduced cell metastatic and invasion ability compared with mock transfected cells in vitro. Overexpression of CMTM5 also suppressed xenograft tumour growth in vivo in a HCC xenograft model. Reduced cell growth and metastasis ability mediated by CMTM5 overexpression was associated with downregulation of PI3K/AKT and its downstream Bcl2, cyclinD1, cyclinE, MMP2 and MMP9 expressions, and an upregulation of p21, Bax, Bad, cleaved caspase3 expressions.ConclusionsOur data suggest that CMTM5 might function as a tumour suppressor in human HCC, and represent a valuable potential therapeutic target for HCC.

Highlights

Human chemokine like factor (CKLF)-like MAL and related proteins for vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been shown to involved and may function as a tumour suppressor in tumorigenesis
CMTM5 expression is downregulated in hepatocellular carcinoma (HCC) tissues and cell lines The CMTM5 expression was examined by immunohistochemistry staining in 76 paired tumour and adjacent normal liver tissues
To further confirm the above results, we examined the expression of CMTM5 in four HCC cell lines (Huh7, Hep3B, HepG2 and SMMC-7721) and one normal liver cell line (L02)

Summary

Introduction

Human chemokine like factor (CKLF)-like MAL and related proteins for vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been shown to involved and may function as a tumour suppressor in tumorigenesis. The current study aimed to investigate the expression and function of CMTM5 in human hepatocellular carcinoma (HCC). Liver cancer is a common malignant and the fourth leading cause of cancer deaths in China [1]. It is estimated 466,100 new cases of liver cancer in 2015 in China, with 422,100 new deaths due to this disease [1]. Hepatocellular carcinoma (HCC) is the most common type and accounts for 70–85%of liver cancer [2]. HCC can be treated with surgery, either removing part of the liver or transplantation, with 5-year survival rates that exceed 70%. Cannot have surgical treatment and so the overall 5-year survival is about 15% [3]. It is important to understand the molecular mechanisms involved in HCC carcinogenesis, and find novel approaches that can effectively inhibit HCC cell growth and metastasis

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