Tripartite motif 31 drives gastric cancer cell proliferation and invasion through activating the Wnt/β-catenin pathway by regulating Axin1 protein stability

Abstract

AbstractMounting evidence has proposed the importance of the Wnt/β-catenin pathway and tripartite motif 31 (TRIM31) in certain malignancies. Our research aimed to clarify the correlation between aberrant TRIM31 expression and the Wnt/β-catenin pathway during gastric cancer (GC) oncogenesis and development. TRIM31 was drastically elevated in GC tissues and was closely associated with aggressive clinical outcomes and poor prognosis. Moreover, TRIM31 downregulation attenuated GC cell proliferation and invasion in vitro. Mechanistically, TRIM31 could bind and ubiquitinate Axin1 protein, thereby facilitating the activation of the Wnt/β-catenin pathway. Additionally, Axin1 knockdown partially abrogated the inhibitory effects on the proliferative, invasive and migratory abilities of GC cells induced by TRIM31 silencing. Furthermore, TRIM31 was negatively correlated with Axin1 protein expression in GC tissues. In summary, we revealed a new TRIM31-Axin1-Wnt/β-catenin axis that contributed greatly to the progression of GC, and targeting this regulatory axis may represent an effective treatment for GC patients.