FOXC2 promotes colorectal cancer proliferation through inhibition of FOXO3a and activation of MAPK and AKT signaling pathways

• FOXC2 expression and localization are valuable markers of colorectal cancer prognosis.
• FOXC2 promotes cell proliferation through activation of MAPK and AKT pathways.
• FOXC2 nuclear localization is required for its promotion of cell proliferation.

Abnormal expression of FOXC2 has been found in several human cancers. However, the role of FOXC2 in the progression of colorectal cancer (CRC) has not been well characterized. In analysis of 206 CRC specimens, we revealed that both high expression and nuclear localization of FOXC2 were correlated to aggressive characteristics and poor survival of patients with CRC. FOXC2 promoted cell proliferation through activation of MAPK and AKT pathways, subsequently down-regulating p27, up-regulating cyclin D1 and p-FOXO3a. Furthermore, FOXC2 nuclear localization was required for its promotion of cell proliferation. These findings suggest that FOXC2 plays an essential role in CRC progression and may serve as a valuable clinical prognostic marker of this disease.