OncoTargets and Therapy (Aug 2019)
GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway
Abstract
GuiYuan Liu,1 Yi Pang,1 YaJun Zhang,2 HaiRong Fu,1 Wei Xiong,1 YongHui Zhang11Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, Chongqing 404120, People’s Republic of China; 2Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, Chongqing 402160, People’s Republic of ChinaCorrespondence: YongHui ZhangChongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, 366 Tianxing Road, Wan Zhou, Chongqing 404120, People’s Republic of ChinaTel +1 858 095 1210Email [email protected]: Gap junction beta-4 protein (GJB4), or connexin 30.3, a member of integral membrane proteins, has been shown to involve and may function as a tumor promoter in tumorigenesis. However, the role of GJB4 in gastric cancer (GC) is still unclear.Materials and methods: We used Progression-free survival Kaplan-Meier analysis and Western blot analysis to detect the expression of GJB4 in GC tissues and cells. In addition, both in vitro and in vivo assays were used to determine the effect of GJB4 on malignant behavior in GC cells.Results: We found that GJB4 was overexpressed in gastric cancer tissues and cells compared with normal tissues and cells. The high GJB4 expression was significantly associated with poor overall survival of GC patients. Knocking down GJB4 in GC cells significantly suppressed cell proliferation and migration. We found that the effects of GJB4-knockdown on GC cells were associated with downregulation of CTNNB1 and its downstream MYC, MMP7 and CCND1 expression. In addition, we found that the promotive effect of GJB4 overexpression on cell proliferation and migration was negated by XAV-939, which is the inhibitor of Wnt/CTNNB1 pathway. Therefore, we revealed a novel mechanism by which GJB4 could activate the Wnt/CTNNB1 pathway to promote GC cell’s proliferation and migration.Conclusion: This study offer insights into GJB4 function and indicate that GJB4 is a promising biomarker and therapeutic target for gastric cancer patients.Keywords: GJB4, cell proliferation, migration, gastric cancer, CTNNB1
