ArticleAmerican journal of cancer research2019
Methionine restriction activates the integrated stress response in triple-negative breast cancer cells by a GCN2- and PERK-independent mechanism.
Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Methionine restriction for cancer therapy: From preclinical studies to clinical trials.Cancer pathogenesis and therapy · 2026Review
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Both asparagine and proline are required to decreaseBiomedical reports · 2025Article
- Bioorthogonal Non-Canonical Amino Acid Tagging (BONCAT) to detect newly synthesized proteins in cells and their secretome.PloS one · 2025Article
- Rescue of Methionine Dependence by Cobalamin in a Human Colorectal Cancer Cell Line.Nutrients · 2024Article
- Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade.Nature communications · 2023Article
- The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction inFrontiers in cell and developmental biology · 2023Article
- Targeting the methionine addiction of cancer.American journal of cancer research · 2022Review
- Article
- Differences in cell death in methionine versus cysteine depletion.Environmental and molecular mutagenesis · 2021Article
- Bruceae Fructus Oil Inhibits Triple-Negative Breast Cancer by Restraining Autophagy: Dependence on the Gut Microbiota-Mediated Amino Acid Regulation.Frontiers in pharmacology · 2021Article
- Review
- Article
- Methionine Restriction and Cancer Biology.Nutrients · 2020Review
- Ultra-low Concentrations of Cisplatinum Down to the ICIn vivo (Athens, Greece)Article
- The Combination of Methionine Adenosyltransferase 2A (MAT2A) Inhibitor AG-270 and Recombinant Methioninase Is Not Cancer-selective in a Co-culture Model of Colon Cancer Cells and Normal Fibroblasts.Cancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Transformed cells are often selectively susceptible to depletion of the amino acid methionine, which induces growth arrest and/or apoptosis. In non-transformed cells, amino acid deficiency is sensed by two stress-activated kinases, general control nonderepressible 2 (GCN2) and protein kinase R-like endoplasmic reticulum kinase (PERK), which phosphorylate and inactivate elongation initiation factor 2 α (eIF2α), thereby suppressing global mRNA translation and inducing activated transcription factor (ATF4). ATF4 and its downstream transcriptional targets including Sestrin-2 constitute an adaptive integrated stress response. We postulated that methionine depletion activates the integrated stress response in breast cancer cells by a GCN2- and/or PERK-dependent mechanism and that selective disruption of one or both of these kinases would enhance the therapeutic activity of methionine restriction. Here we demonstrate that methionine restriction induces eIF2α phosphorylation and enhances ATF4 gene expression and protein levels of ATF4 and Sestrin-2 in triple (ER/PR/HER2)-negative breast cancer (TNBC) cells. However, knockdown of GCN2, PERK or both in TNBC cells did not prevent induction of ATF4 or Sestrin-2 by methionine restriction. In contrast, deletion of
Indexed as
Identifiers
31497357PMC6726988W2991220972What OpenQuestion holds
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.