Oncotarget

Research Papers:

The G-protein-coupled bile acid receptor Gpbar1 (TGR5) suppresses gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway

Cong Guo, Jia Su, Zhijun Li, Rui Xiao, Jianxun Wen, Yanyan Li, Meng Zhang, Xueting Zhang, Donna Yu, Wendong Huang, Wei-Dong Chen and Yan-Dong Wang _

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Oncotarget. 2015; 6:34402-34413. https://doi.org/10.18632/oncotarget.5353

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Abstract

Cong Guo1, Jia Su1, Zhijun Li2, Rui Xiao2, Jianxun Wen2, Yanyan Li3, Meng Zhang1, Xueting Zhang1, Donna Yu4, Wendong Huang4, Wei-Dong Chen2,3, Yan-Dong Wang1

1State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China

2Key Laboratory of Molecular Pathology, School of basic medical science, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P. R. China

3Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, Henan, P. R. China

4Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA

Correspondence to:

Yan-Dong Wang, e-mail: [email protected]

Wei-Dong Chen, e-mail: [email protected]

Keywords: Gpbar1, TGR5, gastric cancer, STAT3, bile acid receptor

Received: April 13, 2014     Accepted: September 11, 2015     Published: September 21, 2015

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.


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