ArticleEMBO molecular medicine2021
CRISPR screens identify tumor-promoting genes conferring melanoma cell plasticity and resistance.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Genome-Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- CASER: A semi-supervised model with multi-omics data integration prioritizes cancer-associated epigenetic regulator genes.PLoS computational biology · 2026Article
- Research hotspots and trends of immunotherapy and melanoma: A bibliometric analysis during 2014-2024.Human vaccines & immunotherapeutics · 2025Article
- Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance.Cells · 2025Review
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.Cell death & disease · 2024Article
- Engineering CRISPR/Cas9 therapeutics for cancer precision medicine.Frontiers in genetics · 2024Review
- Clonal dynamics limits detection of selection in tumour xenograft CRISPR/Cas9 screens.Cancer gene therapy · 2023Article
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- Quantitative landscapes reveal trajectories of cell-state transitions associated with drug resistance in melanoma.iScience · 2022Article
- The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma.EMBO molecular medicine · 2022Article
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
- Ten Years of CRISPRing Cancers In Vitro.Cancers · 2022Review
- Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.Signal transduction and targeted therapy · 2022Review
- Common computational tools for analyzing CRISPR screens.Emerging topics in life sciences · 2021Review
- Article
- Systems-level network modeling deciphers the master regulators of phenotypic plasticity and heterogeneity in melanoma.iScience · 2021Article
- CRISPR screens identify tumor-promoting genes conferring melanoma cell plasticity and resistance.EMBO molecular medicine · 2021Article
- NRF2 Enables EGFR Signaling in Melanoma Cells.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most genetic alterations that drive melanoma development and resistance to targeted therapy have been uncovered. In contrast, and despite their increasingly recognized contribution, little is known about the non-genetic mechanisms that drive these processes. Here, we performed in vivo gain-of-function CRISPR screens and identified SMAD3, BIRC3, and SLC9A5 as key actors of BRAFi resistance. We show that their expression levels increase during acquisition of BRAFi resistance and remain high in persister cells and during relapse. The upregulation of the SMAD3 transcriptional activity (SMAD3-signature) promotes a mesenchymal-like phenotype and BRAFi resistance by acting as an upstream transcriptional regulator of potent BRAFi-resistance genes such as EGFR and AXL. This SMAD3-signature predicts resistance to both current melanoma therapies in different cohorts. Critically, chemical inhibition of SMAD3 may constitute amenable target for melanoma since it efficiently abrogates persister cells survival. Interestingly, decrease of SMAD3 activity can also be reached by inhibiting the Aryl hydrocarbon Receptor (AhR), another druggable transcription factor governing SMAD3 expression level. Our work highlights novel drug vulnerabilities that can be exploited to develop long-lasting antimelanoma therapies.
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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.