ArticleLife science alliance2022
DUSP4 protects BRAF- and NRAS-mutant melanoma from oncogene overdose through modulation of MITF.
Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- DUSP6 is upregulated in metastasis and influences migration and metabolism in pancreatic cancer cells.Scientific reports · 2025Article
- The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.Nature genetics · 2025Article
- Exploiting Paradoxical Activation of Oncogenic MAPK Signaling by Targeting Mitochondria to SensitizeInternational journal of molecular sciences · 2025Article
- SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers.Nature communications · 2024Article
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Drug dependence in cancer is exploitable by optimally constructed treatment holidays.Nature ecology & evolution · 2024Article
- Harnessing the power of AI in precision medicine: NGS-based therapeutic insights for colorectal cancer cohort.Frontiers in oncology · 2024Article
- Identification of DUSP4/6 overexpression as a potential rheostat to NRAS-induced hepatocarcinogenesis.BMC cancer · 2023Article
- ERK mediates interferon gamma-induced melanoma cell death.Molecular cancer · 2023Article
- BRAFScience advances · 2023Article
- Trametinib-Resistant Melanoma Cells Displaying MITFInternational journal of molecular sciences · 2023Article
- An integrative analysis of the single-cell transcriptome identifies DUSP4 as an exhaustion-associated gene in tumor-infiltrating CD8+ T cells.Functional & integrative genomics · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MAPK inhibitors (MAPKi) remain an important component of the standard of care for metastatic melanoma. However, acquired resistance to these drugs limits their therapeutic benefit. Tumor cells can become refractory to MAPKi by reactivation of ERK. When this happens, tumors often become sensitive to drug withdrawal. This drug addiction phenotype results from the hyperactivation of the oncogenic pathway, a phenomenon commonly referred to as oncogene overdose. Several feedback mechanisms are involved in regulating ERK signaling. However, the genes that serve as gatekeepers of oncogene overdose in mutant melanoma remain unknown. Here, we demonstrate that depletion of the ERK phosphatase, DUSP4, leads to toxic levels of MAPK activation in both drug-naive and drug-resistant mutant melanoma cells. Importantly, ERK hyperactivation is associated with down-regulation of lineage-defining genes including
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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 Socratic graph.