MassIVE MSV000084140

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Quantitative Time-Course Profiling of Sorafenib-Treated Hepatocellular Carcinoma (HCC) Cells Through Phosphoproteome Analysis

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Description

Ferroptosis is a new form of regulated, non-apoptotic cell death characterized by excessive lipid peroxidation upon loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4). Sorafenib, an FDA-approved multi-kinase inhibitor drug for treatment of hepatocellular carcinoma (HCC), has been shown to induce ferroptosis. Protein phosphorylation changes upon Sorafenib treatment have been previously reported in patient studies and in cell culture however the early phosphorylation changes during induction of ferroptosis are not completely understood. This work highlights these changes through a time course from 7 to 60 min of Sorafenib treatment in SKHep1 cells to provide insight on the induction of ferroptosis. 6,186 unique phosphosites were quantified from 2,381 phosphoproteins in this study and phosphorylation changes occurred in as early as 30 minutes of Sorafenib treatment. By 60 minutes, significant changes in key regulatory pathways were identified, including sites from ferroptosis-related proteins, indicating the involvement of phospho-regulated signaling during ferroptosis induction. [doi:10.25345/C5V089] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: ferroptosis ; proteomics ; phosphoproteomics ; mass spectrometry ; hepatocellular carcinoma

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Principal Investigators:
(in alphabetical order) 		Lewis Brown, Columbia University, United States
Submitting User: egwerth
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