Tissue transglutaminase-2 promotes gastric cancer progression via the ERK1/2 pathway
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Xiaofeng Wang1,*, Zhenjia Yu1,*, Quan Zhou1, Xiongyan Wu1, Xuehua Chen1, Jianfang Li1, Zhenggang Zhu1, Bingya Liu1 and Liping Su1
1 Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
* These authors have contributed equally to this work
Liping Su, email:
Keywords: TG2, gastric cancer, ERK1/2, tumor progression
Received: August 26, 2015 Accepted: January 04, 2016 Published: January 11, 2016
Gastric cancer (GC) is one of the most common tumors worldwide and involves extensive local tumor invasion, metastasis, and poor prognosis. Understanding mechanisms regulating progression of GC is necessary for developing effective therapeutic strategies. Tissue transglutaminase-2 (TG2), a multifunctional member of the transglutaminase family, has been shown to be critical for tumor initiation and progression. However, how TG2 promotes the progression of GC is unknown. We report that TG2 was highly expressed in GC tissues and positively associated with depth of tumor invasion and late TNM stage. With gain- and loss-of-function approaches, we observed that TG2 promoted GC cell proliferation, migration, invasion, as well as tumorigenesis and peritoneal metastasis in vivo. These events were associated with the ERK1/2 pathway activation and an ERK1/2 inhibitor (U0126) inhibited cell proliferation, migration, and invasion induced by overexpression of TG2. In summary, 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.
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