ArticleNature communications2023
Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications.Oncology research · 2026Review
- A methyl-to-acetyl switch in H3K27 drives metabolic reprogramming and resistance to BRAFNeoplasia (New York, N.Y.) · 2025Article
- Therapeutic Use of Integrin Signaling in Melanoma Cells: Physical Link with the Extracellular Matrix (ECM).Cancers · 2025Review
- Exploring the causal relationship between hemoglobin and pancreatic cancer and its potential mechanisms through bioinformatics and Mendelian randomization.Discover oncology · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Metabolic insights into tumor lymph node metastasis in melanoma.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis.International journal of molecular sciences · 2024Review
- Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling.Genes & diseases · 2024Article
- Feedforward cysteine regulation maintains melanoma differentiation state and limits metastatic spread.Cell reports · 2024Article
- Elucidating the Role of Lipid-Metabolism-Related Signal Transduction and Inhibitors in Skin Cancer.Metabolites · 2024Review
- Association of lipid-lowering drug targets with risk of cutaneous melanoma: a mendelian randomization study.BMC cancer · 2024Article
- Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines.Biomedicines · 2024Article
- Causal effects of lipid-lowering drugs on skin diseases: a two-sample Mendelian randomization study.Frontiers in medicine · 2024Article
- Integrative Multi-Omics Analysis of Oncogenic EZH2 Mutants: From Epigenetic Reprogramming to Molecular Signatures.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
While targeted treatment against BRAF(V600E) improve survival for melanoma patients, many will see their cancer recur. Here we provide data indicating that epigenetic suppression of PGC1α defines an aggressive subset of chronic BRAF-inhibitor treated melanomas. A metabolism-centered pharmacological screen further identifies statins (HMGCR inhibitors) as a collateral vulnerability within PGC1α-suppressed BRAF-inhibitor resistant melanomas. Lower PGC1α levels mechanistically causes reduced RAB6B and RAB27A expression, whereby their combined re-expression reverses statin vulnerability. BRAF-inhibitor resistant cells with reduced PGC1α have increased integrin-FAK signaling and improved extracellular matrix detached survival cues that helps explain their increased metastatic ability. Statin treatment blocks cell growth by lowering RAB6B and RAB27A prenylation that reduces their membrane association and affects integrin localization and downstream signaling required for growth. These results suggest that chronic adaptation to BRAF-targeted treatments drive novel collateral metabolic vulnerabilities, and that HMGCR inhibitors may offer a strategy to treat melanomas recurring with suppressed PGC1α 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.