TRAF6 promoted the metastasis of esophageal squamous cell carcinoma.

Esophageal cancer is one of the most aggressive malignancies and has been ranked as the sixth leading cause of cancer-related death in the world. It is very urgent to find new therapeutic targets. Although tumor necrosis factor receptor-associated factor 6 (TRAF6) was initially identified as an adaptor for NF-κB signaling, recently it has been found to be involved in cancer by modulating various signaling pathways. In the previous study, we have found that TRAF6 promoted the growth of esophageal squamous cell carcinoma (ESCC) cell in vitro and in vivo. However, the effects of TRAF6 on the migration and metastasis of ESCC cells are poorly understood. Here, we found that TRAF6 promoted migration and metastasis of ESCC cells through modulating Ras signaling. Overexpression of TRAF6 promoted the migration of ESCC cells and immortalized esophageal epithelial cells, while knock down the expression of TRAF6 inhibited the migration and metastasis of ESCC cells in vitro and in vivo. Mechanically, TRAF6 binds Ras with its N-terminal and activated Ras signaling. Taken together, TRAF6 played an important role in the metastasis of ESCC and might be a promising therapeutic target.