ArticleAnnals of surgical oncology2023
Conjugated Bile Acids Accelerate Progression of Pancreatic Cancer Metastasis via S1PR2 Signaling in Cholestasis.
Article in Annals of surgical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- The bile acid TUDCA promotes chemoresistance and predicts survival through MAPK signaling in pancreatic ductal adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.Gut microbes · 2025Review
- Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8NPJ biofilms and microbiomes · 2025Article
- Taurochenodeoxycholic acid as a sensitive stratification marker for HBV-associated hepatic cirrhosis status has a hepatoprotective effect.Scientific reports · 2025Article
- Cannabidiol Is Associated with Improved Survival in Pancreatic Cancer and Modulation of Bile Acids and Gut Microbiota.International journal of molecular sciences · 2025Article
- S1PR3 inhibition impairs cell cycle checkpoint via the AKT/WEE1 pathway in oral squamous cell carcinoma.Journal of translational medicine · 2025Article
- An integrative multi-omics analysis reveals a multi-analyte signature of pancreatic ductal adenocarcinoma in serum.Journal of gastroenterology · 2025Article
- Gut Microbiome and Bile Acid Interactions: Mechanistic Implications for Cholangiocarcinoma Development, Immune Resistance, and Therapy.The American journal of pathology · 2025Review
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Targeting sphingosine 1-phosphate and sphingosine kinases in pancreatic cancer: mechanisms and therapeutic potential.Cancer cell international · 2024Review
- Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases.International journal of molecular sciences · 2024Review
- Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development.Pharmacological reviews · 2024Review
- Bile Acids in Pancreatic Carcinogenesis.Metabolites · 2024Review
- The Role of Bile Acids in Pancreatic Cancer.Current cancer drug targets · 2024Review
- Multi-omics reveals the alleviating effect of berberine on ulcerative colitis through modulating the gut microbiome and bile acid metabolism in the gut-liver axis.Frontiers in pharmacology · 2024Article
- S1PR2 participates in intestinal injury in severe acute pancreatitis by regulating macrophage pyroptosis.Frontiers in immunology · 2024Article
- Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy.International journal of molecular sciences · 2023Review
- Review
- Sphingosine 1-phosphate receptor 2 promotes the onset and progression of non-alcoholic fatty liver disease-related hepatocellular carcinoma through the PI3K/AKT/mTOR pathway.Discover oncology · 2023Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundPancreatic cancer (PC) has an extremely high mortality rate, where obstructive jaundice due to cholestasis is a classic symptom. Conjugated bile acids (CBAs) such as taurocholic acid (TCA) have been reported to activate both the ERK1/2 and AKT signaling pathways via S1P receptor 2 (S1PR2) and promote growth of cholangiocarcinoma. Thus, we hypothesize that CBAs, which accumulate in cholestasis, accelerate PC progression via S1PR2.
methodsMurine Panc02-luc and human AsPC-1, MIA PaCa2, and BxPC-3 cells were treated with TCA, S1PR2 agonist CYM5520, S1PR2 antagonist JTE-013, sphingosine-1-phosphate (S1P), and functional S1P receptor antagonist (except S1PR2) FTY720. Bile duct ligation (BDL) was performed on liver implantation or intraperitoneal injection of Panc02-luc cells.
resultsPanc02-luc and AsPC-1 cells predominantly expressed S1PR2, and their growth and migration were stimulated by TCA or CYM5520 in dose-dependent manner, which was blocked by JTE-013. This finding was not seen in PC cell lines expressing other S1P receptors than S1PR2. Panc02-luc growth stimulation by S1P was not blocked by FTY720. BDL significantly increased PC liver metastasis compared with sham. PC peritoneal carcinomatosis was significantly worsened by BDL, confirmed by number of nodules, tumor weight, bioluminescence, Ki-67 stain, ascites, and worse survival compared with sham. CYM5520 significantly worsened PC carcinomatosis, whereas treatment with anti-S1P antibody or FTY720 also worsened progression.
conclusionsCBAs accelerated growth of S1PR2 predominant PC both in vitro and in vivo. This finding implicates S1PR2 as a potential therapeutic target in metastatic S1PR2 predominant pancreatic cancer.
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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.