ArticleCell death & disease2023
SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 85 citations in OpenAlex.
- Magnetoreceptor Promotes Hepatocellular Carcinoma Development and Blunts Sorafenib-Induced Ferroptosis by Regulating Iron Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic polymorphisms in the SLC27A5 gene are associated with biochemical characteristics of HBV patients in Yunnan.Journal of applied biomedicine · 2026Article
- SLC25A45 as a prognostic biomarker promotes malignant progression via mutant p53 in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Article
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- AMBRA1 activation alleviates zearalenone-induced swine testicular cell ferroptosis by facilitating mitophagy.Journal of animal science and biotechnology · 2026Article
- Unlocking the Secrets of Regulated Cell Death in Large B-Cell Lymphoma Beyond Apoptosis: Signaling Pathways and Therapeutic Options.International journal of molecular sciences · 2026Review
- Radiotherapy combined with anti-PD-1 immunotherapy promotes ferroptosis-driven control of hepatocellular carcinoma.Genes and immunity · 2026Article
- Development of Gold coated calcium peroxide nanoparticles for photothermal ferroptosis against skin cancer and C. albicans.Communications chemistry · 2026Article
- Machine Learning-Based Diagnostic Models for Early Gastric Cancer Using Clinical Laboratory Indicators.International journal of general medicine · 2026Article
- Ferroptosis in liver diseases: molecular mechanisms, biomarker potential, and clinical translation.Frontiers in cell and developmental biology · 2026Review
- SLC27, solute carrier 27 family, a long-chain fatty acid membrane transporters, in human cancers.Frontiers in cell and developmental biology · 2026Review
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- Identification and Validation of the Prognostic Value of PTTG1-Related Genes in Hepatocellular Carcinoma by Mendelian Randomization and Single-Cell Transcriptome Analysis.Iranian journal of biotechnology · 2026Article
- Emerging small molecule strategies target cancer stem cells through ferroptosis and metabostemness.Discover oncology · 2025Review
- Review
- Long non-coding RNA LINC01532 sustains redox homeostasis and accelerates lenvatinib resistance in hepatocellular carcinoma.Journal of advanced research · 2025Article
- Ozonated olive oil inhibits melanoma proliferation by inducing ferroptosis.Biochemistry and biophysics reports · 2025Article
- Article
- Ferroptosis and cancer: when iron turns against tumors.Cellular and molecular life sciences : CMLS · 2025Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance.
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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.