ArticleNature communications2021
The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution.Nature cell biology · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Therapy-induced cholesterol biosynthesis drives lung cancer dormancy and drug resistance.The Journal of clinical investigation · 2026Article
- Targeting the epigenome and the integrated stress response to normalize colorectal cancer subclonal plasticity and progression.Cell death & disease · 2026Article
- Article
- The Janus framework of the integrated stress response: from homeostasis to maladaptation.Life science alliance · 2026Review
- Identification and validation of prognostic genes associated with integrative stress response in lung adenocarcinoma and construction of the risk models.Scientific reports · 2026Article
- [Expression, Prognostic and Functional Analysis of SRSF Family Proteins in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation.Nature genetics · 2026Article
- Epithelial and microenvironmental mosaicism under stress: a two-compartment model for lung cancer development in never-smokers.Frontiers in cell and developmental biology · 2026Review
- Integrative Single-Cell and Spatial Transcriptomics Reveal Organelle Stress-Associated Heterogeneity and Immune Microenvironment Remodeling in Lung Adenocarcinoma.Human mutation · 2026Article
- Endoplasmic reticulum stress-related genes play a role in the prognosis of lung adenocarcinoma.Discover oncology · 2025Article
- AND logic-gated CRISPR/Cas9 and hybridization chain reaction system for precise ctDNA detection.Journal of nanobiotechnology · 2025Article
- Mammalian mitohormesis: from mitochondrial stressors to organismal benefits.The EMBO journal · 2025Review
- Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression.Antioxidants (Basel, Switzerland) · 2025Review
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- The Integrated Stress Response Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer.Cancer research · 2025Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 7 countries.
Funding
Abstract
The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2α), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2α causes the translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a suitable therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a rationale for the implementation of ISR-based regimens in LUAD treatment.
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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.