Abstract
Epithelial–mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well‐differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1‐medicated Wnt/β‐catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer.
Highlights
Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1, 2]
We found that the levels of TIPE1 were significantly reduced and were inversely correlated with differentiation status and distant metastasis in patients with primary gastric cancer
We found that TIPE1 negatively regulated cell invasion and metastasis capacities in gastric cancer cells
Summary
Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1, 2]. It is urgent to identify novel molecular markers and explore related molecular mechanisms contributing to improving diagnostic and therapeutic management of gastric cancer. The main reasons for failure and mortality of gastric cancer are cell infiltration and metastasis. Mounting evidence has indicated that EMT plays an important role in the invasiveness and metastasis of gastric cancer cells by the dissolution of cell–cell junctions and the development of individual motile mesenchymal cells with increased mobility [3, 4]. During EMT, gastric cancer cells can obtain the stem cell properties which are closely a 2017 The Authors
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