ArticleCell death discovery2021
ABCA8-mediated efflux of taurocholic acid contributes to gemcitabine insensitivity in human pancreatic cancer via the S1PR2-ERK pathway.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Role of lipid-associated fibroblasts and their signature genes FABP4, CD36 and ABCA8 in gastric cancer progression.Oncology letters · 2026Article
- Review
- Gut microbiota modulation of gastrointestinal cancers: from dysbiosis signatures to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
- ABCA8 drives bone loss via disrupting Th17/Treg imbalance: a novel immunometabolic target for osteoporosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- The bile acid TUDCA promotes chemoresistance and predicts survival through MAPK signaling in pancreatic ductal adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Cancer-associated fibroblasts as key regulators of lipid metabolism in the tumour microenvironment.Oncogene · 2026Review
- Rat Glioma 101.8 Tissue Strain: Molecular and Morphological Features.International journal of molecular sciences · 2025Article
- Cannabidiol Is Associated with Improved Survival in Pancreatic Cancer and Modulation of Bile Acids and Gut Microbiota.International journal of molecular sciences · 2025Article
- Growth Hormone Signaling in Bladder Cancer: Transcriptomic Profiling of Patient Samples and In Vitro Evidence of Therapy Resistance via ABC Transporters and EMT Activation.International journal of molecular sciences · 2025Article
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
- ABCA8 Elevation Predicts the Prognosis and Exerts the Anti-oncogenic Effects on the Malignancy of Non-small Cell Lung Cancer via TCF21-Mediated Inactivation of PI3K/AKT.Molecular biotechnology · 2025Article
- 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
- Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.International journal of molecular sciences · 2024Article
- Article
- Article
- Bioinformatics and Experimental Study Revealed LINC00982/ miR-183-5p/ABCA8 Axis Suppresses LUAD Progression.Current cancer drug targets · 2024Article
- The Role of Bile Acids in Pancreatic Cancer.Current cancer drug targets · 2024Review
- Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer.Cancers · 2023Article
- Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The development of resistance to anticancer drugs is believed to cause chemotherapy failure in pancreatic cancer (PC). The efflux of anticancer drugs mediated by ATP-binding cassette (ABC) transporters is a widely accepted mechanism for chemoresistance, but for ABCA subfamily members, which are characterized by their ability to transport lipids and cholesterol, its role in chemoresistance remains unknown. Here we found that the expression of ABCA8, a member of ABCA subfamily transporters, was significantly increased in human PC cells after gemcitabine (GEM) treatment, as well as in established GEM-resistant (Gem-R) PC cells. Importantly, ABCA8 knockdown reversed the chemoresistance phenotype of Gem-R cells, whereas ABCA8 overexpression significantly decreased the sensitivity of human PC cells to GEM, both in vitro and in vivo, demonstrating an important role of ABCA8 in regulating chemosensitivity. Moreover, our results showed that treatment with taurocholic acid (TCA), an endogenous substrate of ABCA8, also induced GEM insensitivity in PC cells. We further demonstrated that ABCA8 mediates the efflux of TCA out of PC cells, and that extracellular TCA activates extracellular signal-regulated kinase (ERK) signaling via the sphingosine 1-phosphate receptor 2 (S1PR2), which is responsible for ABCA8-induced GEM ineffectiveness. Together, these findings reveal a novel TCA-related mechanism of ABCA subfamily transporter-mediated chemoresistance that goes beyond the role of a drug pump and suggest ABCA8 or the TCA-S1RP2-ERK pathway as potential targets for improving the effectiveness of and overcoming the resistance to chemotherapy in PC.
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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.