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

摘要

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.