ArticleiScience2020
Disrupting ATF4 Expression Mechanisms Provides an Effective Strategy for BRAF-Targeted Melanoma Therapy.
Article in iScience, 2020. 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, 18 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- mTOR inhibition enhances the antitumor efficacy of pan-RAF-MEK blockade by inhibiting the ATF4-MTHFD2 pathway.Cell death & disease · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability.Cancer research · 2025Article
- MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability.bioRxiv : the preprint server for biology · 2024Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Activating mutations in EGFR and PI3K promote ATF4 induction for NSCLC cell survival during amino acid deprivation.Heliyon · 2023Article
- Elucidation of an mTORC2-PKC-NRF2 pathway that sustains the ATF4 stress response and identification of Sirt5 as a key ATF4 effector.Cell death discovery · 2022Article
- Spautin-1 inhibits mitochondrial complex I and leads to suppression of the unfolded protein response and cell survival during glucose starvation.Scientific reports · 2022Article
- Connecting Metabolic Rewiring With Phenotype Switching in Melanoma.Frontiers in cell and developmental biology · 2022Review
- Noncoding RNAs: emerging players in skin cancers pathogenesis.American journal of cancer research · 2021Article
- NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma.Pharmaceuticals (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRAF V600 mutation influences cellular signaling pathways for melanoma development. However, the role of oncogenic BRAF in adaptive stress response pathways is not fully understood. Here, we show that oncogenic BRAF plays an essential role in the induction of ATF4 following the activation of general control non-derepressible 2 (GCN2) kinase during nutrient stress and BRAF-targeted, therapeutic stress. Under GCN2 activation, BRAF ensures ATF4 induction by utilizing mTOR and eIF4B as downstream regulators. In contrast to the MEK-ERK pathway, this signaling pathway remains temporarily active even during treatment with BRAF inhibitors, thereby enabling the transient induction of ATF4. We also identify a chemical compound that prevents BRAF inhibitor-induced activation of the GCN2-ATF4 pathway and produces synergistic cell killing with BRAF inhibitors. Our findings establish a collaborative relationship between oncogenic BRAF and the GCN2-ATF4 signaling pathway, which may provide a novel therapeutic approach to target the adaptive stress response.
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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.