ArticleActa pharmacologica Sinica2023
Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 83 citations in OpenAlex.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- Ferroptosis regulatory networks as therapeutic sensitizers in combination therapy for hepatocellular carcinoma (Review).Oncology letters · 2026Review
- The novel oleanolic acid derivative ZQL-4c modulates trastuzumab resistance in HER2+ breast cancer by inhibiting SCD-mediated lipid metabolism disorders.Cancer cell international · 2026Article
- Ferroptosis vulnerability of enzalutamide resistant prostate cancer conferred by ACSL4 overexpression and GPX4 antagonism.Cell death & disease · 2026Article
- Biomimetic β-lapachone and hemin nanoassembly for intracellular oxidation cascade amplified ferroptosis in hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2026Article
- LAMTOR5 promotes hepatoma growth in mice by disrupting LC3-p62-mediated autophagy and preventing p62 proteasome degradation.Acta pharmacologica Sinica · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Silencing progestagen-associated endometrial protein (PAEP) suppresses sorafenib resistance and enhances sorafenib-induced ferroptosis in hepatocellular carcinoma.Liver research (Beijing, China) · 2026Article
- Reprogrammed Lipid Metabolism as a Gatekeeper of Hepatocarcinogenesis: from Enzyme Regulation to Precision Therapy.Current oncology reports · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Identification of key ferroptosis-related targets in colorectal cancer: A transcriptomics-driven study via machine learning and AUcell analysis of single-cell RNA-sequencing.Journal of Cancer · 2026Article
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications.Oncology research · 2026Review
- Magnolol triggers ferroptosis in triple-negative breast cancer through modulation of the ETS2/SLC7A11/GPX4 signaling axis.Frontiers in pharmacology · 2026Article
- DCUN1D5 as a New Biomarker and Regulator of Fatty Acid Metabolism in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Ferroptosis-The "Double-Edged Sword" in Cancer: Mechanisms of Tumor Suppression/Resistance and Therapeutic Manipulation.Biology · 2025Review
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib, which inhibits multiple kinases, is an effective frontline therapy for hepatocellular carcinoma (HCC). Ferroptosis is a form of iron-dependent programmed cell death regulated by lipid peroxidation, which can be induced by sorafenib treatment. Oncoprotein hepatitis B X-interacting protein (HBXIP) participates in multiple biological pro-tumor processes, including growth, metastasis, drug resistance, and metabolic reprogramming. However, the role of HBXIP in sorafenib-induced ferroptotic cell death remains unclear. In this study, we demonstrated that HBXIP prevents sorafenib-induced ferroptosis in HCC cells. Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced HCC cell death. Interestingly, suppression of HBXIP increased malondialdehyde (MDA) production and glutathione (GSH) depletion to promote sorafenib-mediated ferroptosis and cell death. Ferrostatin-1, a ferroptosis inhibitor, reversed the enhanced anticancer effect of sorafenib caused by HBXIP silencing in HCC cells. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis. Functionally, activation of the HBXIP/SCD axis reduced the anticancer activity of sorafenib and suppressed ferroptotic cell death in vivo and in vitro. HBXIP/SCD axis-mediated ferroptosis can serve as a novel downstream effector of sorafenib. Our results provide new evidence for clinical decisions in HCC therapy.
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