期刊
ONCOTARGET
卷 6, 期 33, 页码 34402-34413出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5353
关键词
Gpbar1; TGR5; gastric cancer; STAT3; bile acid receptor
资金
- National Natural Science Foundation of China [81370537, 81270522, 81472232, 81260269]
- Fundamental Research Funds for the Central Universities [YS1407, 2050205]
- Program for Science & Technology Innovation Talents in Universities of Henan Province (HASTIT) [13HASTIT024]
- Plan for Scientific Innovation Talent of Henan Province
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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