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Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

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

Authors: Gang Xu, Chengxue Dang

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

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).

Methods

CMTM5 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.

Results

CMTM5 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.

Conclusions

Our data suggest that CMTM5 might function as a tumour suppressor in human HCC, and represent a valuable potential therapeutic target for HCC.
Appendix
Available only for authorised users
Literature
1.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRefPubMed
2.
3.
Kanda T, Ogasawara S, Chiba T, Haga Y, Omata M, Yokosuka O. Current management of patients with hepatocellular carcinoma. World J Hepatol. 2015;7(15):1913–20.CrossRefPubMedPubMedCentral
4.
Han W, Ding P, Xu M, Wang L, Rui M, Shi S, Liu Y, Zheng Y, Chen Y, Yang T, et al. Identification of eight genes encoding chemokine-like factor superfamily members 1–8 (CKLFSF1-8) by in silico cloning and experimental validation. Genomics. 2003;81(6):609–17.CrossRefPubMed
5.
Wang L, Wu C, Zheng Y, Qiu X, Wang L, Fan H, Han W, Lv B, Wang Y, Zhu X, et al. Molecular cloning and characterization of chemokine-like factor super family member 1 (CKLFSF1), a novel human gene with at least 23 alternative splicing isoforms in testis tissue. Int J Biochem Cell Biol. 2004;36(8):1492–501.CrossRefPubMed
6.
Shao L, Cui Y, Li H, Liu Y, Zhao H, Wang Y, Zhang Y, Ng KM, Han W, Ma D, et al. CMTM5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines. Clin Cancer Res. 2007;13(19):5756–62.CrossRefPubMed
7.
Li H, Guo X, Shao L, Plate M, Mo X, Wang Y, Han W. CMTM5-v1, a four-transmembrane protein, presents a secreted form released via a vesicle-mediated secretory pathway. BMB Rep. 2010;43(3):182–7.CrossRefPubMed
8.
Shao L, Guo X, Plate M, Li T, Wang Y, Ma D, Han W. CMTM5-v1 induces apoptosis in cervical carcinoma cells. Biochem Biophys Res Commun. 2009;379(4):866–71.CrossRefPubMed
9.
Guo X, Li T, Wang Y, Shao L, Zhang Y, Ma D, Han W. CMTM5 induces apoptosis of pancreatic cancer cells and has synergistic effects with TNF-alpha. Biochem Biophys Res Commun. 2009;387(1):139–42.CrossRefPubMed
10.
Niu J, Li H, Zhang Y, Li J, Xie M, Li L, Qin X, Qin Y, Guo X, Jiang Q, et al. Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia. Leuk Res. 2011;35(6):771–6.CrossRefPubMed
11.
Li P, Liu K, Li L, Yang M, Gao W, Feng J, Lv Y, Qu X, Kong B. Reduced CMTM5 expression correlates with carcinogenesis in human epithelial ovarian cancer. Int J Gynecol Cancer. 2011;21(7):1248–55.PubMed
12.
Zhang H, Nan X, Li X, Chen Y, Zhang J, Sun L, Han W, Li T. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma. Biochem Biophys Res Commun. 2014;447(2):304–10.CrossRefPubMed
13.
Xiao Y, Yuan Y, Zhang Y, Li J, Liu Z, Zhang X, Sheng Z, Xu T, Wang X. CMTM5 is reduced in prostate cancer and inhibits cancer cell growth in vitro and in vivo. Clin Transl Oncol. 2015;17(6):431–7.CrossRefPubMed
14.
Liu B, Su Y, Li T, Yuan W, Mo X, Li H, He Q, Ma D, Han W. CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation. Oncotarget. 2015;6(38):41092–107.CrossRefPubMedPubMedCentral
15.
Li H, Li J, Su Y, Fan Y, Guo X, Li L, Su X, Rong R, Ying J, Mo X, et al. A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth. Oncogene. 2014;33(24):3109–18.CrossRefPubMed
16.
Yuan W, Li T, Mo X, Wang X, Liu B, Wang W, Su Y, Xu L, Han W. Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Oncotarget. 2016;7(20):29507–19.CrossRefPubMedPubMedCentral
17.
Zhang W, Mendoza MC, Pei X, Ilter D, Mahoney SJ, Zhang Y, Ma D, Blenis J, Wang Y. Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling. J Biol Chem. 2012;287(15):11850–8.CrossRefPubMedPubMedCentral
18.
Metadata
Title
CMTM5 is downregulated and suppresses tumour growth in hepatocellular carcinoma through regulating PI3K-AKT signalling
Authors
Gang Xu
Chengxue Dang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0485-8

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