FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1.

FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1.
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FoxM1通过靶向Snai1促进肝细胞癌上皮间质转化

DOI:
10.3892/mmr.2017.7223
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发表时间:
2017-10
影响因子:
3.4
通讯作者:
Liang J
Liang J
中科院分区:
医学4区
文献类型:
--
作者:
Yu CP;Yu S;Shi L;Wang S;Li ZX;Wang YH;Sun CJ;Liang J

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叉头盒蛋白M1(Forkhead box protein M1,FoxM 1)在多种恶性肿瘤中表达异常,在肿瘤转移中起重要作用。癌细胞的上皮-间质转化(EMT)与肿瘤转移密切相关,但FoxM 1在EMT中的作用及其在肿瘤转移中的调控作用尚不清楚。在本研究中,FoxM 1,Snai 1和E-cadherin的表达在肝细胞癌(HCC)细胞系与各种转移潜力,并在正常肝细胞,采用蛋白质印迹分析和逆转录定量聚合酶链反应。使用伤口愈合和Transwell迁移测定来评估FoxM 1对HCC细胞的侵袭和迁移能力的影响。结果显示,FoxM 1在肝癌细胞中的表达明显高于正常肝细胞(P<0.05)。此外,FoxM 1的表达在MHCC-LM 3细胞中显著增加,其特征在于具有较高的转移潜力,与SMMC-7721细胞相比,SMMC-7721细胞具有较低的转移潜力。FoxM 1与E-cadherin表达呈负相关(P<0.05),与Snai 1表达呈正相关(P<0.05)。这些观察结果表明,FoxM 1可以增强癌细胞的侵袭和迁移,从而促进其EMT,其机制可能涉及Snai 1的调节。因此,可以假设FoxM 1有潜力作为一种新的诊断标志物和治疗肝癌患者的治疗靶点。
Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial-mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E-cadherin in hepatocellular carcinoma (HCC) cell lines with various metastatic potentials, and in normal liver cells, was investigated using western blot analysis and reverse transcription-quantitative polymerase chain reaction. The effects of FoxM1 on the invasive and migratory capabilities of HCC cells were evaluated using wound healing and Transwell migration assays. The present results demonstrated that FoxM1 expression was significantly upregulated in HCC cells compared with in normal hepatocytes (P<0.05). In addition, FoxM1 expression was significantly increased in MHCC-LM3 cells, characterized by higher metastatic potential, compared with in SMMC-7721 cells, which have a lower metastatic potential. Furthermore, overexpression of FoxM1 was demonstrated to be negatively correlated with E-cadherin (P<0.05) and positively associated with Snai1 (P<0.05) expression. These observations suggested that FoxM1 may enhance the invasion and migration of cancer cells, and thus promotes their EMT, in a mechanism that may involve the regulation of Snai1. Therefore, it may be hypothesized that FoxM1 has potential as a novel diagnostic marker and therapeutic target for the treatment of patients with HCC.
悬浮在胶原蛋白凝胶中的上皮可以失去极性,并表达迁移间充质细胞的特征。
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