title: The G-protein-coupled bile acid receptor Gpbar1 (TGR5) suppresses gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway.
abstract: Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well known for its roles in regulation of energy homeostasis and glucose metabolism. Here we show that TGR5 is a suppressor of gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway. We firstly show that TGR5 activation greatly inhibited proliferation and migration of human gastric cancer cells and strongly induced gastric cancer cell apoptosis. We then found that TGR5 activation antagonized STAT3 signaling pathway through suppressing the phosphorylation of STAT3 and its transcription activity induced by lipopolysaccharide (LPS) or interleukin-6. TGR5 overexpression with ligand treatment inhibited gene expression mediated by STAT3. It suggests that TGR5 antagonizes gastric cancer proliferation and migration at least in part by inhibiting STAT3 signaling. These findings identify TGR5 as a suppressor of gastric cancer cell proliferation and migration that may serve as an attractive therapeutic tool for human gastric cancer.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Su
authors.affiliation: Key Laboratory of Molecular Pathology, School of basic medical science, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P. R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Pathology, School of basic medical science, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Molecular Pathology, School of basic medical science, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P. R. China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Wen
authors.affiliation: Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, Henan, P. R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Molecular Pathology, School of basic medical science, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P. R. China.|Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, Henan, P. R. China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Yan-Dong
authors.initials: YD
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
chemical_list: C473772:GPBAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor
keywords: Gpbar1; STAT3; TGR5; bile acid receptor; gastric cancer