Dawei Li, Qingguo Li, Ye Xu, Changhua Zhuo, Sanjun Cai

 Department of Colorectal Surgery, Shanghai Cancer Center

Objective:For khead box protein C2 (FOXC2) plays a vital role in the carcinogenesis of some malignances. However, its clinicopathologic significance and prognostic value in colon cancer remain unclear. In this study, we aim to investigate the expression and significance of FOXC2 involved in the progression. Method: FOXC2 expression was analyzed in a tissue microarray (TMA) containing 185 samples of primary colon cancer tumor samples and in human colon cancer cell lines. The effect of FOXC2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo. Result: FOXC2 was overexpressed in human colon cancer cells and tissues, and correlated with colon cancer progression and patient survival. Functional study demonstrated that FOXC2 promoted cell growth, cell migration, and tumor formation in nude mice, whereas knock down of FOXC2 by short hairpin RNA (shRNAs) significantly suppressed cell growth, cell migration and tumor formation. Further study found that FOXC2 enhanced AKT activity with subsequent GSK-3β phosphorylation and Snail stabilization, and then induced epithelial-mesenchymal transition (EMT) and promoted tumor invasion and metastasis. Conclusion: FOXC2 promotes colon cancer metastasis by facilitating EMT and acts as apotential prognostic factor and therapeutic target in colon cancer.

Key Words: colon cancer  metastasis  FOXC2