ArticleOncotarget2016
The bile acid receptor GPBAR1 (TGR5) is expressed in human gastric cancers and promotes epithelial-mesenchymal transition in gastric cancer cell lines.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Meta-Analysis Reveals the Prognostic Relevance of Nuclear and Membrane-Associated Bile Acid Receptors in Gastric Cancer.Clinical and translational gastroenterology · 2021Pooled it
- The Farnesoid X receptor-bile acid axis contributes to immune evasion in gastric cancer and its inhibition enhances efficacy of anti-PD-L1 therapy.Biochemistry and biophysics reports · 2026Article
- Gut microbiota-metabolism axis in digestive tumors: Emerging targets for novel therapies (Review).Experimental and therapeutic medicine · 2026Review
- Association of serum bile acid profiles with the risk of gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus.World journal of diabetes · 2026Article
- Impact of Cholecystectomy on Gastric Mucosal c-MYC and h-TERT Expression; A Potential Link to Gastric Cancer Development.Balkan journal of medical genetics : BJMG · 2025Article
- Gut Feelings: How Microbes, Diet, and Host Immunity Shape Disease.Biomedicines · 2025Review
- Molecular mechanisms of metastatic peritoneal dissemination in gastric adenocarcinoma.Cancer metastasis reviews · 2025Review
- Crosstalk between bile acids and gut microbiota: a potential target for precancerous lesions of gastric cancer.Frontiers in pharmacology · 2025Review
- Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition.bioRxiv : the preprint server for biology · 2024Article
- Role of the Microbiome in the Diagnosis and Management of Gastroesophageal Cancers.Journal of gastrointestinal cancer · 2024Review
- Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers.Microorganisms · 2024Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Review
- Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer.Translational andrology and urology · 2022Article
- Structural basis and molecular mechanism of biased GPBAR signaling in regulating NSCLC cell growth via YAP activity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Investigation of the potential role of TGR5 in pancreatic cancer by a comprehensive molecular experiments and the liquid chromatography mass spectrometry (LC-MS) based metabolomics.Discover oncology · 2022Article
- Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori-induced inflammation-driven gastric carcinogenesis.The Journal of clinical investigation · 2022Article
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer.Molecular medicine reports · 2022Article
- GPBAR1 promotes proliferation and is related to poor prognosis of high-grade glioma via inducing MAFB expression.Histology and histopathology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GPBAR1 (also known as TGR5) is a bile acid activated receptor expressed in several adenocarcinomas and its activation by secondary bile acids increases intestinal cell proliferation. Here, we have examined the expression of GPBAR1 in human gastric adenocarcinomas and investigated whether its activation promotes the acquisition of a pro-metastatic phenotype. By immunohistochemistry and RT-PCR analysis we found that expression of GPBAR1 associates with advanced gastric cancers (Stage III-IV). GPBAR1 expression in tumors correlates with the expression of N-cadherin, a markers of epithelial-mesenchymal transition (EMT) (r=0.52; P<0.01). Expression of GPBAR1, mRNA and protein, was detected in cancer cell lines, with MKN 45 having the higher expression. Exposure of MKN45 cells to GPBAR1 ligands, TLCA, oleanolic acid or 6-ECDCA (a dual FXR and GPBAR1 ligand) increased the expression of genes associated with EMT including KDKN2A, HRAS, IGB3, MMP10 and MMP13 and downregulated the expression of CD44 and FAT1 (P<0.01 versus control cells). GPBAR1 activation in MKN45 cells associated with EGF-R and ERK1 phosphorylation. These effects were inhibited by DFN406, a GPBAR1 antagonist, and cetuximab. GPBAR1 ligands increase MKN45 migration, adhesion to peritoneum and wound healing. Pretreating MKN45 cells with TLCA increased propensity toward peritoneal dissemination in vivo. These effects were abrogated by cetuximab. In summary, we report that GPBAR1 is expressed in advanced gastric cancers and its expression correlates with markers of EMT. GPBAR1 activation in MKN45 cells promotes EMT. These data suggest that GPBAR1 antagonist might have utility in the treatment of gastric cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.