ArticleJournal of experimental & clinical cancer research : CR2022
Cholesterol sensor SCAP contributes to sorafenib resistance by regulating autophagy in hepatocellular carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Role of SCAP in regulation of pancreatic homeostasis, pancreatitis, and tumorigenesis.Oncogene · 2026Article
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Revisiting cholesterol metabolism in hepatocellular carcinoma: a hidden driver of systemic therapy response.ESMO gastrointestinal oncology · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Targeting MED8 enhances sorafenib sensitivity in hepatocellular carcinoma by disrupting epithelial-mesenchymal transition mechanisms.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- RhoE downregulation leads to enhanced cholesterol biosynthesis and sorafenib resistance in hepatocellular carcinoma.The Journal of biological chemistry · 2025Article
- Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance.Hepatology communications · 2025Review
- SLC25A39 regulates Hedgehog signaling to promote tumor progression and sorafenib resistance in hepatocellular carcinoma.Scientific reports · 2025Article
- TCF12 enhances angiogenesis and affects sorafenib response in liver cancer via HIF-1α interaction.Biomolecules & biomedicine · 2025Article
- Accumulation of microtubule-associated protein tau promotes hepatocellular carcinogenesis through inhibiting autophagosome-lysosome fusion.Molecular and cellular biochemistry · 2025Article
- Novel Strategies against Hepatocellular Carcinoma through Lipid Metabolism.Oncology research · 2025Review
- Sorafenib-induced macrophage extracellular traps via ARHGDIG/IL4/PADI4 axis confer drug resistance through inhibiting ferroptosis in hepatocellular carcinoma.Biology direct · 2024Article
- Uncover the anticancer potential of lycorine.Chinese medicine · 2024Review
- Introducing urea into tirapazamine derivatives to enhance anticancer therapy.National science review · 2024Article
- Decreased lncRNA HNF4A-AS1 facilitates resistance to sorafenib-induced ferroptosis of hepatocellular carcinoma by reprogramming lipid metabolism.Theranostics · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Exploration of ANKRD27 as an immune-related prognostic factor in pan-cancer and hepatocellular carcinoma.Frontiers in oncology · 2024Article
- GPAT3 is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma.Theranostics · 2024Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is one of the most malignant tumors and the fourth leading cause of cancer-related death worldwide. Sorafenib is currently acknowledged as a standard therapy for advanced HCC. However, acquired resistance substantially limits the clinical efficacy of sorafenib. Therefore, further investigations of the associated risk factors are highly warranted.
methodsWe analysed a group of 78 HCC patients who received sorafenib treatment after liver resection surgery. The expression of SCAP and its correlation with sorafenib resistance in HCC clinical samples were determined by immunohistochemical analyses. Overexpression and knockdown approaches in vitro were used to characterize the functional roles of SCAP in regulating sorafenib resistance. The effects of SCAP inhibition in HCC cell lines were analysed in proliferation, apoptosis, and colony formation assays. Autophagic regulation by SCAP was assessed by immunoblotting, immunofluorescence and immunoprecipitation assays. The combinatorial effect of a SCAP inhibitor and sorafenib was tested using nude mice.
resultsHypercholesterolemia was associated with sorafenib resistance in HCC treatment. The degree of sorafenib resistance was correlated with the expression of the cholesterol sensor SCAP and consequent deposition of cholesterol. SCAP is overexpressed in HCC tissues and hepatocellular carcinoma cell lines with sorafenib resistance, while SCAP inhibition could improve sorafenib sensitivity in sorafenib-resistant HCC cells. Furthermore, we found that SCAP-mediated sorafenib resistance was related to decreased autophagy, which was connected to decreased AMPK activity. A clinically significant finding was that lycorine, a specific SCAP inhibitor, could reverse acquired resistance to sorafenib in vitro and in vivo.
conclusionsSCAP contributes to sorafenib resistance through AMPK-mediated autophagic regulation. The combination of sorafenib and SCAP targeted therapy provides a novel personalized treatment to enhance sensitivity in sorafenib-resistant HCC.
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