Abstract
PURPOSE: Our previous study proved that FOXM1 regulates colorectal cancer (CRC) cell metastasis through epithelial-mesenchymal transition program. The aim of this study is to further explore the underlying mechanism of FOXM1 in CRC. MATERIALS AND METHODS: In this study, we detected the mRNA and protein expressions of FOXM1 and β-catenin in CRC tissues and their corresponding normal-appearing tissues (NATs) by quantitative reverse transcription-PCR and western blot analysis, respectively. Then the potential link between FOXM1 and β-catenin in CRC tissues was analyzed. Furthermore, we systematically analyzed the biological functions of FOXM1 in CRC cells after reconstitution of FOXM1 expression in vitro. Moreover, the mechanism of FOXM1-promoted CRC progression by improving β-catenin nuclear translocation was also discussed. RESULTS: Our data demonstrated that FOXM1 and β-catenin were upregulated in CRC tissues compared with the corresponding NATs (P<0.05). Clinicopathologic analysis revealed that increased FOXM1 (or β-catenin) expression positively correlated with some clinicopathologic features, such as tumor size, TNM stage, lymphatic metastasis, and distant metastasis (P<0.05). Meanwhile, the possible relationships between FOXM1 and β-catenin in CRC samples were evaluated using SPSS software, and a significant positive correlation was found (P<0.05). In vitro data demonstrate that elevated FOXM1 expression exerted oncogenic effects on CRC via activation of β-catenin signaling pathway. The inhibition of β-catenin by siRNAs significantly attenuates FOXM1-induced malignant activities. CONCLUSION: The data suggested that FOXM1/β-catenin is critical for malignancy of CRC, which may constitute a potential therapeutic strategy for CRC.