CMTM5 is downregulated and suppresses tumour growth in hepatocellular carcinoma through regulating PI3K-AKT signalling.
CMTM5 is downregulated and suppresses tumour growth in hepatocellular carcinoma through regulating PI3K-AKT signalling.
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DOI：
10.1186/s12935-017-0485-8
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发表时间：
2017
影响因子：
5.8
通讯作者：
Dang C
中科院分区：
文献类型：
--
作者：
Xu G;Dang C
人趋化因子样因子（CKLF）样MAL和囊泡转运跨膜相关蛋白，含结构域的成员5（CMTM 5）已被证明参与肿瘤发生并可能作为肿瘤抑制因子起作用。本研究旨在探讨CMTM 5在人肝细胞癌（HCC）中的表达及功能。应用免疫组化方法检测76例HCC组织中CMTM 5的表达，并分析其临床意义。通过体外和体内实验研究了CMTM 5在细胞增殖、凋亡和侵袭中的作用及其分子机制。CMTM 5在HCC组织和细胞系中表达显著下调。77.6%的肝癌组织中CMTM 5蛋白表达缺失，而正常肝组织中CMTM 5蛋白表达缺失率仅为3.9%。CMTM 5低表达与HCC患者的总生存率显著相关（P = 0.009）。在Huh 7细胞中恢复CMTM 5的表达显著抑制细胞生长，促进细胞凋亡，并降低细胞的转移和侵袭能力。在HCC异种移植模型中，CMTM 5的过表达也抑制了体内异种移植肿瘤的生长。CMTM 5过表达介导的细胞生长和转移能力降低与PI 3 K/AKT及其下游Bcl 2、cyclinD 1、cyclinE、MMP 2和MMP 9表达下调以及p21、Bax、Bad、cleaved caspase 3表达上调有关。我们的数据表明，CMTM 5可能作为一个肿瘤抑制剂在人类肝癌，并代表了一个有价值的潜在的治疗肝癌的目标。本文的在线版本（10.1186/s12935-017-0485-8）包含补充材料，可供授权用户使用。
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). 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. 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. Our data suggest that CMTM5 might function as a tumour suppressor in human HCC, and represent a valuable potential therapeutic target for HCC. The online version of this article (10.1186/s12935-017-0485-8) contains supplementary material, which is available to authorized users.
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影响因子：
2.9
作者：
Mittal S;El-Serag HB
通讯作者：
El-Serag HB
影响因子：
3.8
作者：
Li, Henan;Guo, Xiaohuan;Han, Wenling
通讯作者：
Han, Wenling
DOI：
10.1016/j.bbrc.2009.06.148
发表时间：
2009-09-11
影响因子：
3.1
作者：
Guo, Xiaohuan;Li, Ting;Han, Wenling
通讯作者：
Han, Wenling
CMTM5-v1 诱导宫颈癌细胞凋亡。
DOI：
10.1016/j.bbrc.2008.12.126
发表时间：
2009-02-20
影响因子：
3.1
作者：
Shao, Luning;Guo, Xiaohuan;Han, Wenling
通讯作者：
Han, Wenling
CMTM7 敲低通过减少 Rab5 激活来增加人类非小细胞肺癌细胞的致瘤性和 EGFR-AKT 信号传导。
影响因子：
--
作者：
Liu B;Su Y;Li T;Yuan W;Mo X;Li H;He Q;Ma D;Han W
通讯作者：
Han W