Gastric cancer is one of the most common tumors worldwide with extensive local tumor invasion, metastasis and poor prognosis. Thus, understanding the mechanisms regulating progression of gastric cancer is the key for developing effective therapeutic strategies. Tissue tranglutaminase-2 (TG2), a multifunctional member of the transglutaminase (TGase) family, has already been proved to play an important role in tumor initiation and progression. However, the specific role and underlying molecular mechanisms of TG2 in the progression of gastric cancer (GC) remain unknown. Here we showed that TG2 was highly expressed in GC tissues and positively associated with depth of tumor invasion and late TNM stage. With gain and lose-of function approaches, we found that TG2 promotes GC cell proliferation, migration and invasion, as well as tumorigenesis and peritoneal metastasis in vivo. These events were associated with activating of ERK1/2 pathway, and ERK1/2 inhibitor U0126 inhibited cell proliferation, migration and invasion induced by overexpression of TG2. Taken together, these findings suggest that TG2 contributes to tumorigenesis and progression of GC by activating the ERK1/2 signaling pathway and is a potential therapeutic target of metastatic gastric cancer.

Citation Format: Liping Su, Xiaofeng Wang, Quan Zhou, Xiongyan Wu, Bingya Liu. Tissue tranglutaminase-2 promotes gastric cancer progression via ERK1/2 pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 945.