4-1BBL Promoted the Proliferation and Migration of Human Gastric Cancer Cells through Wnt/p-catenin Signaling Pathway / 中国生物化学与分子生物学报

ABSTRACT

4-IBB and 4-IBB ligand (4-1BBL) , also known as CI) 137 and CD 137 ligand, are members of tumor necrosis factor (TNF) receptor and ligand family, respectively.The interaction of 4-1BBL and 4-IBB can activate T cell immune response.Therefore, 4-1BBL has been playing a role as a classical costimulatory molecule involving in anti-tumor immune responses.In recent decades, it was reported that 4-1BBL had multiple functions in tumor cells.However, the molecular mechanism of 4-1BBL in the progression of gastric cancer (GC) remains unclear.This study investigated the biological function and molecular mechanism of 4-1BBL in human GC cells.First, analysis from TCGA and Kaplan Meier plotter databases showed that 4-1BBL expression level in GC tissues was significantly higher than that in adjacent tissues (P<0.001) , and 4-1BBL high expression was positively associated with poor prognosis of GC (P<0.05).Knockout of 4-1BBL significantly inhibited the proliferation (P<0.05) , invasion and migration of GC cells (P<0.05 ) , and increased the apoptosis of GC cells (P<0.05).Western blot showed that 4- 1 BBL knockout decreased the protein expression levels of (3-catenin, c-Myc and Cyclin D1, and blocked Wnt/p-catenin signaling pathway.On the contrary, 4-1 BBL overexpression significantly promoted the proliferation (P<0.05) , invasion and migration of GC cells (P<0.05) , and reduced the apoptosis of GC cells (P<0.05).Moreover, 4-1 BBL overexpression increased the protein expression levels of (3- catenin, c-Myc and Cyclin D1, and activated Wnt/p-catenin signaling pathway.In summary, 4-1 BBL promoted the proliferation and migration of human GC cells through Wnt/(B-catenin signaling pathway.