FOXM1 promotes the growth and metastasis of colorectal cancer via activation of β-catenin signaling pathway

Kankan Yang,1,* Bing Jiang,1,* Yecai Lu,1,* Qingbing Shu,1 Pan Zhai,1 Qiaoming Zhi,2 Qixin Li1 1Department of Gastrointestinal Surgery, Chaohu Hospital of Anhui Medical University, Hefei 238000, Anhui, China; 2Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China *These authors contributed equally to this work 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. Keywords: FOXM1, β-catenin, colorectal cancer, signaling pathwa