Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells.
Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells.
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DOI：
10.1002/2211-5463.12254
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发表时间：
2017-08
期刊：
影响因子：
2.6
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Hu K;Huang P;Luo H;Yao Z;Wang Q;Xiong Z;Lin J;Huang H;Xu S;Zhang P;Liu B
哺乳动物激活蛋白（MENA）是一种影响细胞运动和粘附的肌动蛋白调节蛋白。已知它在肝细胞癌（HCC）的致瘤性中起作用，但其潜在的分子机制仍不清楚。本研究旨在研究MENA的致癌潜力及其调节HCC细胞中癌症干细胞（CSC）样表型的能力。分别使用真实的-time-PCR和western blot评估人HCC组织标本和HCC细胞系中靶基因的mRNA和蛋白水平。从HCC细胞系产生稳定的MENA过表达HCC细胞。采用Transwell细胞迁移和集落形成试验评价致瘤性。MENA的异位表达显著增强HCC细胞中的细胞迁移和集落形成能力。MENA的过表达上调了HCC细胞中的几种肝祖细胞/干细胞标志物。高MENA蛋白水平与人HCC组织中MENA、CD 133、细胞角蛋白19（CK 19）和上皮细胞粘附分子（EpCAM）的高mRNA水平相关。MENA的过表达增强了HCC细胞中上皮间质转化（EMT）标志物、细胞外信号调节激酶（ERK）磷酸化和β-连环蛋白的水平。该研究表明，MENA在HCC细胞中的过表达促进了干细胞标志物、EMT标志物和致瘤性。这些作用可能至少部分涉及ERK和β-连环蛋白信号通路。
Mammalian‐enabled (MENA) protein is an actin‐regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma (HCC) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell (CSC)‐like phenotypes in HCC cells. Real‐time‐PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively. Stable MENA‐overexpressing HCC cells were generated from HCC cell lines. Transwell cell migration and colony formation assays were employed to evaluate tumorigenicity. Ectopic expression of MENA significantly enhanced cell migration and colony‐forming ability in HCC cells. Overexpression of MENA upregulated several hepatic progenitor/stem cell markers in HCC cells. A high MENA protein level was associated with high mRNA levels of MENA, CD133, cytokeratin 19 (CK19), and epithelial cell adhesion molecule (EpCAM) in human HCC tissues. Overexpression of MENA enhanced epithelial‐to‐mesenchymal transition (EMT) markers, extracellular signal‐regulated kinases (ERK) phosphorylation, and the level of β‐catenin in HCC cells. This study demonstrated that overexpression of MENA in HCC cells promoted stem cell markers, EMT markers, and tumorigenicity. These effects may involve, at least partially, the ERK and β‐catenin signaling pathways.
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