ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed.
- Targeting SQLE-Mediated Cholesterol Metabolism to Promote Oxidative Stress and Attenuate Drug Resistance in Osteosarcoma.Antioxidants (Basel, Switzerland) · 2026Article
- Deep chemical structure graph learning deciphers the lipotoxicity code of hypertriglyceridemic pancreatitis.NPJ digital medicine · 2026Article
- Association between cholesterol and liver injury risk in solid cancer patients treated with PD-1 inhibitors: evidence from two cohort studies.BMC cancer · 2026Article
- Article
- Response mechanism of hepatorenal metabolic barrier function to drugs and environmental poisons and intervention strategy of natural products.Frontiers in pharmacology · 2026Review
- Ginsenoside 20(S)-Rg3 upregulates SQLE to reprogram cholesterol metabolism of ovarian cancer cells.iScience · 2025Article
- Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The inducible role of autophagy in cell death: emerging evidence and future perspectives.Cell communication and signaling : CCS · 2025Review
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Authors and funding
15 authors.
Funding
Abstract
Metabolic disorders have been identified as one of the causes of drug-induced liver injury; however, the direct regulatory mechanism regarding this disorder has not yet been clarified. In this study, a single regulatory mechanism of small molecule kinase inhibitors, with crizotinib as the representative drug is elucidated. First, it is discovered that crizotinib induced aberrant lipid metabolism and apoptosis in the liver. A mechanistic study revealed that crizotinib treatment promoted the accumulation of squalene epoxidase (SQLE) by inhibiting autophagosome-lysosome fusion which blocked the autophagic degradation of SQLE. A maladaptive increase in SQLE led to disturbances in cholesterol and sphingolipid metabolism via an enzymatic activity-dependent manner. Abnormal cholesterol results in both steatosis and inflammatory infiltration, and disturbances in sphingolipid metabolism promote cell apoptosis by inducing lysosomal membrane permeabilization. The restoration of the level or activity of SQLE ameliorated steatosis and hepatocyte injury. The autophagy activator known as metformin or the SQLE enzymatic inhibitor known as terbinafine has potential clinical use for alleviating crizotinib hepatotoxicity.
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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.