DEC1 mediates IL-6-induced EMT in CRC via PI3K/AKT/NF-κB activation.

Abstract

Colorectal cancer (CRC) represents a leading global malignancy. This study investigated the role of differentiated embryonic chondrocyte expressed gene 1 (DEC1) in interleukin-6 (IL-6)-induced invasion and migration of CRC. In vitro, IL-6 upregulated DEC1 expression and modulated the levels of epithelial-to-mesenchymal transition (EMT)-associated proteins in CRC cells. DEC1 overexpression amplified the IL-6-induced invasion and migration phenotypes, increasing the expression of N-cadherin and vimentin but reducing E-cadherin expression. Conversely, DEC1 knockdown attenuated these phenotypes, decreasing the expression of N-cadherin and vimentin but increasing E-cadherin expression. These findings suggest that IL-6 induced EMT through increasing DEC1. Moreover, DEC1 overexpression increased the levels of basal and IL-6-stimulated phosphatidylinositol 3 kinase (PI3K) p110α, p-Akt, and p-p65, indicating activation of the PI3K/Akt/NF-κB signaling pathway. Conversely, DEC1 knockdown diminished these effects. Notably, treatment with the inhibitor LY294002 or the NF-κB inhibitor EVP4593 significantly reversed the IL-6-induced upregulation of DEC1, the increase in N-cadherin and vimentin, and the reduction in E-cadherin. These in vitro findings were further corroborated in vivo. Dec1 ^+/+ CRC mice exhibited elevated Il6 mRNA levels and enhanced tumor invasion compared with Dec1 ^-/- CRC mice. Dec1 deficiency increased E-cadherin and decreased N-cadherin and vimentin, accompanied by inhibition of the PI3K/Akt/NF-κB signaling pathway in mice. Taken together, our results demonstrate that DEC1 mediates IL-6-induced invasion and migration of CRC via activation of the PI3K/Akt/NF-κB signaling pathway.