ArticleJournal of experimental & clinical cancer research : CR2018
Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 88 citations in OpenAlex.
- Mechanisms Underlying Cancer Chemoresistance: A Starting Point to Identify New Anticancer Strategies.International journal of molecular sciences · 2026Article
- Decoding the Role of Lipid Metabolism and Membrane Dynamics in Melanoma.International journal of molecular sciences · 2026Review
- Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets.International journal of molecular sciences · 2026Review
- Metabolic Reprogramming in Melanoma: An Epigenetic Point of View.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.Redox biology · 2025Article
- Commentary: Transcription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.Frontiers in pharmacology · 2025Article
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer.Metabolites · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors.Cell death & disease · 2024Article
- Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine.Molecular cancer · 2024Review
- Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells.Cancers · 2024Review
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- Causal role of metabolites in non-small cell lung cancer: Mendelian randomization (MR) study.PloS one · 2024Article
- Skin Anti-Inflammatory Potential with Reduced Side Effects of Novel Glucocorticoid Receptor Agonists.International journal of molecular sciences · 2023Article
- Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed.Science China. Life sciences · 2023Review
- Upregulated expression of miR-4443 and miR-4488 in drug resistant melanomas promotes migratory and invasive phenotypes through downregulation of intermediate filament nestin.Journal of experimental & clinical cancer research : CR · 2023Article
- Toward a Unifying Hypothesis for Redesigned Lipid Catabolism as a Clinical Target in Advanced, Treatment-Resistant Carcinomas.International journal of molecular sciences · 2023Review
- Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics.Journal of hematology & oncology · 2023Review
- BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2023Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundCombination therapy with BRAF and MEK inhibitors significantly improves survival in BRAF mutated melanoma patients but is unable to prevent disease recurrence due to the emergence of drug resistance. Cancer stem cells (CSCs) have been involved in these long-term treatment failures. We previously reported in lung cancer that CSCs maintenance is due to altered lipid metabolism and dependent upon Stearoyl-CoA-desaturase (SCD1)-mediated upregulation of YAP and TAZ. On this ground, we investigated the role of SCD1 in melanoma CSCs.
methodsSCD1 gene expression data of melanoma patients were downloaded from TCGA and correlated with disease progression by bioinformatics analysis and confirmed on patient's tissues by qRT-PCR and IHC analyses. The effects of combination of BRAF/MEKi and the SCD1 inhibitor MF-438 were monitored by spheroid-forming and proliferation assays on a panel of BRAF-mutated melanoma cell lines grown in 3D and 2D conditions, respectively. SCD1, YAP/TAZ and stemness markers were evaluated in melanoma cells and tissues by qRT-PCR, WB and Immunofluorescence.
resultsWe first observed that SCD1 expression increases during melanoma progression. BRAF-mutated melanoma 3D cultures enriched for CSCs overexpressed SCD1 and were more resistant than 2D differentiated cultures to BRAF and MEK inhibitors. We next showed that exposure of BRAF-mutated melanoma cells to MAPK pathway inhibitors enhanced stemness features by upregulating the expression of YAP/TAZ and downstream genes but surprisingly not SCD1. However, SCD1 pharmacological inhibition was able to downregulate YAP/TAZ and to revert at the same time CSC enrichment and resistance to MAPK inhibitors.
conclusionsOur data underscore the role of SCD1 as prognostic marker in melanoma and promote the use of SCD1 inhibitors in combination with MAPK inhibitors for the control of drug resistance.
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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.