FoxM1 is associated with metastasis in colorectal cancer through induction of the epithelial-mesenchymal transition

The aim of the present study was to investigate the role of forkhead box M1 (FoxM1) in epithelial-mesenchymal transition (EMT) and metastasis in colorectal cancer (CRC). Immunohistochemical assays were performed to detect FoxM1 and epithelial (E-) cadherin protein expression in 92 CRC, 61 colonic adenoma and 32 wild-type colonic tissue samples. Quantitative polymerase chain reaction (qPCR) assays were performed to determine the expression levels of FoxM1 and E-cadherin mRNAs in 30 CRC and adjacent normal mucosal tissues. RNA interference was used to knock down endogenous FoxM1 expression in CRC cell lines, and the migratory and invasive capacity of the CRC cells was analyzed. The expression of FoxM1, E-cadherin and neuronal (N-) cadherin in the CRC cell lines was evaluated using qPCR and Western blot analysis. The relative expression levels of FoxM1 mRNA and protein were significantly increased in the CRC tissues compared with those in the colonic adenoma and wild-type mucosal tissue samples (P<0.01). In contrast, the relative expression levels of E-cadherin mRNA and protein were significantly decreased in the CRC tissues compared with in the colonic adenoma and normal mucosal tissues (P<0.01). FoxM1 overexpression and decreased E-cadherin expression were significantly associated with poor colonic tissue differentiation, lymph node metastasis and an advanced tumor-node-metastasis stage. Additionally, the increased expression of FoxM1 was associated with a decrease in E-cadherin expression (P<0.01). Furthermore, RNA interference-mediated FoxM1 knockdown significantly inhibited the proliferation, migration and invasion of CRC cells. Downregulation of FoxM1 expression significantly increased E-cadherin expression and decreased N-cadherin expression. The results of the present study suggest that FoxM1 overexpression in tumor tissues is significantly associated with metastasis in CRC through the induction of EMT.