ArticleMolecular cancer therapeutics2010
Sorafenib activates CD95 and promotes autophagy and cell death via Src family kinases in gastrointestinal tumor cells.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 87 citations in OpenAlex.
- Pharmacogenomic insights: IL-23R and ATG-10 polymorphisms in Sorafenib response for hepatocellular carcinoma.Clinical and experimental medicine · 2025Trial
- The sorafenib plus nutlin-3 combination promotes synergistic cytotoxicity in acute myeloid leukemic cells irrespectively of FLT3 and p53 status.Haematologica · 2012Trial
- Accumulation of microtubule-associated protein tau promotes hepatocellular carcinogenesis through inhibiting autophagosome-lysosome fusion.Molecular and cellular biochemistry · 2025Article
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Let-7a promotes periodontal bone regeneration of bone marrow mesenchymal stem cell aggregates via the Fas/FasL-autophagy pathway.Journal of cellular and molecular medicine · 2023Article
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- Targeting hyaluronic acid synthase-3 (HAS3) for the treatment of advanced renal cell carcinoma.Cancer cell international · 2022Article
- Cholesterol sensor SCAP contributes to sorafenib resistance by regulating autophagy in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Synergistic inhibitory effect of berberine and icotinib on non-small cell lung cancer cells via inducing autophagic cell death and apoptosis.Apoptosis : an international journal on programmed cell death · 2021Article
- Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis.Cell death & disease · 2021Article
- Asah2 Represses the p53-Hmox1 Axis to Protect Myeloid-Derived Suppressor Cells from Ferroptosis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin.Biochemistry and biophysics reports · 2020Article
- Metformin Resensitizes Sorafenib-Resistant HCC Cells Through AMPK-Dependent Autophagy Activation.Frontiers in cell and developmental biology · 2020Article
- p53 at the Crossroads between Different Types of HDAC Inhibitor-Mediated Cancer Cell Death.International journal of molecular sciences · 2019Review
- Kinase inhibitors: look beyond the label on the bottle.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- A Novel Drug Resistance Mechanism: Genetic Loss of Xeroderma Pigmentosum Complementation Group C (Frontiers in pharmacology · 2019Article
- Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53.International journal of molecular sciences · 2018Review
- Article
- [pemetrexed + sildenafil], via autophagy-dependent HDAC downregulation, enhances the immunotherapy response of NSCLC cells.Cancer biology & therapy · 2017Article
- Therapeutic implications of bioactive sphingolipids: A focus on colorectal cancer.Cancer biology & therapy · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Sorafenib and vorinostat interact in a synergistic fashion to kill carcinoma cells by activating CD95; the present studies have determined how sorafenib and vorinostat individually contribute to CD95 activation. Sorafenib (3-6 micromol/L) promoted a dose-dependent increase in Src Y416, ERBB1 Y845 and CD95 Y232/Y291 phosphorylation, and Src Y527 dephosphorylation. Low levels of sorafenib-induced (3 micromol/L) CD95 tyrosine phosphorylation did not promote surface localization whereas sorafenib (6 micromol/L), or sorafenib (3 micromol/L) and vorinostat (500 nmol/L) treatment promoted higher levels of CD95 phosphorylation which correlated with DISC formation, receptor surface localization, and autophagy. CD95 (Y232F, Y291F) was not tyrosine phosphorylated and was unable to localize plasma membrane or induce autophagy. Knockdown/knockout of Src family kinases abolished sorafenib-induced CD95 tyrosine phosphorylation, DISC formation, and the induction of cell death and autophagy. Knockdown of platelet-ived growth factor receptor-beta enhanced Src Y416 and CD95 tyrosine phosphorylation, which correlated with elevated CD95 plasma membrane levels and autophagy, and with a reduced ability of sorafenib to promote CD95 membrane localization. Vorinostat increased reactive oxygen species levels, and in a delayed NF kappa B-dependent fashion, those of FAS ligand and CD95. Neutralization of FAS-L did not alter the initial rapid drug-induced activation of CD95; however, neutralization of FAS-L reduced sorafenib + vorinostat toxicity by approximately 50%. Thus, sorafenib contributes to CD95 activation by promoting receptor tyrosine phosphorylation, whereas vorinostat contributes to CD95 activation via the initial facilitation of reactive oxygen species generation and subsequently of FAS-L expression.
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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.