ArticleGenes & development2017
Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Differentiation state affects PD-L1 expression in cutaneous melanoma: a systematic review.Cellular & molecular biology letters · 2026Pooled it
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses.Molecular therapy. Oncology · 2026Article
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer.Molecular oncology · 2026Review
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Metabolic buffering restricts phenotype switching in melanoma.The EMBO journal · 2026Article
- Selective mRNA translation determines adaptative mutability of melanoma cells to anti-BRAF/MEK combination therapy.EMBO molecular medicine · 2026Article
- scFANCL: Dual contrastive learning with false-negative correction at cell level for single-cell RNA-seq clustering.BMC genomics · 2026Article
- Extracellular matrix stiffness determines the phenotypic behavior of dedifferentiated melanoma cells through a DDR1/2-dependent YAP mechanotransduction pathway.Oncogenesis · 2026Article
- MITF maintains genome stability in nonmelanocyte lineages.Molecular oncology · 2026Article
- Nonsense-mediated mRNA decay: friend or foe in cancer biology?Cell communication and signaling : CCS · 2026Review
- Mathematical modeling of ribosome competition informs testable treatment strategies for drug-tolerant cancer persister cells.iScience · 2026Article
- Current evidence and emerging approaches in immunotherapy for gynecological cancers.Discover oncology · 2026Review
- AhR-dependent ferroptosis as a therapeutic opportunity to counteract BRAFi-resistance in melanoma.Cell death discovery · 2026Article
- Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets.International journal of molecular sciences · 2026Review
- MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma.Cell reports · 2025Article
- SOX10 Regulates Melanoma Metastasis Through the IRF1-ITGA3/EphA2-FAK Pathway.Cancer science · 2025Article
- Antagonistic roles for MITF and TFE3 in melanoma plasticity.Cell reports · 2025Article
- Fatty acid uptake activates an AXL-CAV1-β-catenin axis to drive melanoma progression.Genes & development · 2025Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood. Here we show that microenvironmental cues, including inflammation-mediated resistance to adoptive T-cell immunotherapy, transcriptionally repress MITF via ATF4 in response to inhibition of translation initiation factor eIF2B. ATF4, a key transcription mediator of the integrated stress response, also activates AXL and suppresses senescence to impose the MITF-low/AXL-high drug-resistant phenotype observed in human tumors. However, unexpectedly, without translation reprogramming an ATF4-high/MITF-low state is insufficient to drive invasion. Importantly, translation reprogramming dramatically enhances tumorigenesis and is linked to a previously unexplained gene expression program associated with anti-PD-1 immunotherapy resistance. Since we show that inhibition of eIF2B also drives neural crest migration and yeast invasiveness, our results suggest that translation reprogramming, an evolutionarily conserved starvation response, has been hijacked by microenvironmental stress signals in melanoma to drive phenotypic plasticity and invasion and determine therapeutic outcome.
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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.