DEC2 suppresses tumor proliferation and metastasis by regulating ERK/NF-κB pathway in gastric cancer

Differentiated embryonic chondrocyte expressed gene 2 (DEC2; BHLHE41/Sharp1) is a helix-loop-helix (bHLH) transcription factor, and its deregulation has been observed in several tumors. However, this gene's effects on tumor progression are controversial, and its roles in gastric cancer (GC) remain unclear. In the present study, we found that DEC2 expression level is lower in GC tissues compared with adjacent non-tumor tissues, and negatively correlated with tumor invasion, lymph node metastasis, TNM stage, and poor survival of GC patients. Positive clinical correlations of DEC2 with EMT regulator, E-cadherin, were also observed in the tissue sections. Overexpression of DEC2 inhibits cell proliferation and EMT in vitro, as well as tumor growth and metastasis in vivo. DEC2 expression also induces cell apoptosis. Furthermore, the anti-metastatic effect of DEC2 was mediated by inhibiting ERK/NF-kappa B/EMT axis. After treatment with ERK1/2 chemical inhibitor (U0126), DEC2's inhibitory effect on ERK/NF-kappa B/EMT was further decreased. Collectively, these data helped to characterize DEC2, which might be a potential molecular target for diagnostic and therapeutic approaches for GC.