ArticleeLife2021
Unique integrated stress response sensors regulate cancer cell susceptibility when Hsp70 activity is compromised.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed.
- Targeting HDAC and proteostasis to eradicate quiescent cancer cells.Cancer gene therapy · 2026Article
- Identification of the MRTFA/SRF pathway as a critical regulator of quiescence and chemotherapy resistance in cancer.Cancer letters · 2026Article
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Review
- Article
- Structural insights into allosteric inhibition of HRI kinase by heme binding via HDX-MS.The Biochemical journal · 2025Article
- Role of the NuRD complex and altered proteostasis in cancer cell quiescence.bioRxiv : the preprint server for biology · 2025Article
- Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Translational oncology · 2024Review
- ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.Endocrinology · 2024Article
- Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells.International journal of molecular sciences · 2024Article
- Stress biology: Complexity and multifariousness in health and disease.Cell stress & chaperones · 2024Article
- Heat Shock Proteins and Breast Cancer.International journal of molecular sciences · 2024Review
- Non-Essential Amino Acid Availability Influences Proteostasis and Breast Cancer Cell Survival During Proteotoxic Stress.Molecular cancer research : MCR · 2023Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers.Acta pharmaceutica Sinica. B · 2023Review
- Canonical and Noncanonical ER Stress-Mediated Autophagy Is a Bite the Bullet in View of Cancer Therapy.Cells · 2022Review
- The Anticancer Ruthenium Compound BOLD-100 Targets Glycolysis and Generates a Metabolic Vulnerability towards Glucose Deprivation.Pharmaceutics · 2022Article
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells.Journal of medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Molecular chaperones, such as Hsp70, prevent proteotoxicity and maintain homeostasis. This is perhaps most evident in cancer cells, which overexpress Hsp70 and thrive even when harboring high levels of misfolded proteins. To define the response to proteotoxic challenges, we examined adaptive responses in breast cancer cells in the presence of an Hsp70 inhibitor. We discovered that the cells bin into distinct classes based on inhibitor sensitivity. Strikingly, the most resistant cells have higher autophagy levels, and autophagy was maximally activated only in resistant cells upon Hsp70 inhibition. In turn, resistance to compromised Hsp70 function required the integrated stress response transducer, GCN2, which is commonly associated with amino acid starvation. In contrast, sensitive cells succumbed to Hsp70 inhibition by activating PERK. These data reveal an unexpected route through which breast cancer cells adapt to proteotoxic insults and position GCN2 and autophagy as complementary mechanisms to ensure survival when proteostasis is compromised.
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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 OpenQuestion graph.