ArticleOncogene2016
Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Breast Cancer Progression by the FGF/FGFR Axis: A Metabolic Perspective.Journal of mammary gland biology and neoplasia · 2025Review
- Synergistic Upregulation of Extracellular Vesicles and Cell-Free Nucleic Acids by Chloroquine and Temozolomide in Glioma Cell Cultures.International journal of molecular sciences · 2025Article
- Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion.Breast cancer research : BCR · 2025Article
- METTL16 suppressed the proliferation and cisplatin-chemoresistance of bladder cancer by degrading PMEPA1 mRNA in a m6A manner through autophagy pathway.International journal of biological sciences · 2024Article
- Article
- Altered Lysosomal Function Manipulates Cellular Biosynthetic Capacity By Remodeling Intracellular Cholesterol Distribution.Cell biochemistry and biophysics · 2023Article
- Article
- Integrated proteogenomic characterization of urothelial carcinoma of the bladder.Journal of hematology & oncology · 2022Article
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
- Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes.Frontiers in cardiovascular medicine · 2022Article
- Hydroxychloroquine overcomes cabergoline resistance in a patient with Lactotroph Pituitary neuroendocrine tumor: a case report.Frontiers in endocrinology · 2022Article
- A perspective on the role of autophagy in cancer.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Article
- Lysosomal Biogenesis and Implications for Hydroxychloroquine Disposition.The Journal of pharmacology and experimental therapeutics · 2021Article
- Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity.Frontiers in pharmacology · 2021Review
- Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer.BMC urology · 2020Article
- New drugs are not enough‑drug repositioning in oncology: An update.International journal of oncology · 2020Review
- The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity.Cell death and differentiation · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations to fibroblast growth factor receptor 3 (FGFR3) and phosphatase and tensin homologue (PTEN) signalling pathway components (for example, PTEN loss, PIK3CA, AKT1, TSC1/2) are common in bladder cancer, yet small-molecule inhibitors of these nodes (FGFR/PTENi) show only modest activity in preclinical models. As activation of autophagy is proposed to promote survival under FGFR/PTENi, we have investigated this relationship in a panel of 18 genetically diverse bladder cell lines. We found that autophagy inhibition does not sensitise bladder cell lines to FGFR/PTENi, but newly identify an autophagy-independent cell death synergy in FGFR3-mutant cell lines between mTOR (mammalian target of rapamycin) pathway inhibitors and chloroquine (CQ)-an anti-malarial drug used as a cancer therapy adjuvant in over 30 clinical trials. The mechanism of synergy is consistent with lysosomal cell death (LCD), including cathepsin-driven caspase activation, and correlates with suppression of cSREBP1 and cholesterol biosynthesis in sensitive cell lines. Remarkably, loss of viability can be rescued by saturating cellular membranes with cholesterol or recapitulated by statin-mediated inhibition, or small interfering RNA knockdown, of enzymes regulating cholesterol metabolism. Modulation of CQ-induced cell death by atorvastatin and cholesterol is reproduced across numerous cell lines, confirming a novel and fundamental role for cholesterol biosynthesis in regulating LCD. Thus, we have catalogued the molecular events underlying cell death induced by CQ in combination with an anticancer therapeutic. Moreover, by revealing a hitherto unknown aspect of lysosomal biology under stress, we propose that suppression of cholesterol metabolism in cancer cells should elicit synergy with CQ and define a novel approach to future cancer treatments.
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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.