ArticleOncotarget2017
Inhibition of stress-inducible HSP70 impairs mitochondrial proteostasis and function.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators.Frontiers in cellular neuroscience · 2023Pooled it
- ATP1A3-related syndromes: our case-series unveiling a dynamic, fever-triggered and overlapping array of neurological phenotypes.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- T-2 Toxin Neurotoxicity: Molecular Mechanisms and Emerging Chemoprotective Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Selective Translation Under Heat Shock: Integrating HSP70 mRNA Regulation with Cellular Stress Responses in Yeast and Mammals.Molecular biology of the cell · 2025Review
- Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Changes to the Autophagy-Related Muscle Proteome Following Short-Term Treatment with Ectoine in the Duchenne Muscular Dystrophy Mouse Model mdx.International journal of molecular sciences · 2025Article
- HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer.Cell death and differentiation · 2024Article
- The role of peptides in reversing chemoresistance of breast cancer: current facts and future prospects.Frontiers in pharmacology · 2023Review
- Investigating the Function of Human Jumping Translocation Breakpoint Protein (hJTB) and Its Interacting Partners through In-Solution Proteomics of MCF7 Cells.Molecules (Basel, Switzerland) · 2022Article
- HSP70 alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial dysfunction-initiated NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes.Burns & trauma · 2022Article
- GRPEL2 Knockdown Exerts Redox Regulation in Glioblastoma.International journal of molecular sciences · 2021Article
- Fever supports CD8Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells.Nature communications · 2021Article
- Bioactivity Profiles of Cytoprotective Short-Chain Quinones.Molecules (Basel, Switzerland) · 2021Article
- Macrophage ubiquitin-specific protease 2 contributes to motility, hyperactivation, capacitation, and in vitro fertilization activity of mouse sperm.Cellular and molecular life sciences : CMLS · 2021Article
- Methyl Jasmonate Cytotoxicity and Chemosensitization of T Cell LymphomaFrontiers in pharmacology · 2021Article
- A Novel Inhibitor of HSP70 Induces Mitochondrial Toxicity and Immune Cell Recruitment in Tumors.Cancer research · 2020Article
- Proteotoxic Stress and Cell Death in Cancer Cells.Cancers · 2020Review
- The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways.Molecular and cellular biology · 2019Article
- Tumor cells containing the African-Centric S47 variant ofOncotarget · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Protein quality control is an important component of survival for all cells. The use of proteasome inhibitors for cancer therapy derives from the fact that tumor cells generally exhibit greater levels of proteotoxic stress than do normal cells, and thus cancer cells tend to be more sensitive to proteasome inhibition. However, this approach has been limited in some cases by toxicity to normal cells. Recently, the concept of inhibiting proteostasis in organelles for cancer therapy has been advanced, in part because it is predicted to have reduced toxicity for normal cells. Here we demonstrate that a fraction of the major stress-induced chaperone HSP70 (also called HSPA1A or HSP72, but hereafter HSP70) is abundantly present in mitochondria of tumor cells, but is expressed at quite low or undetectable levels in mitochondria of most normal tissues and non-tumor cell lines. We show that treatment of tumor cells with HSP70 inhibitors causes a marked change in mitochondrial protein quality control, loss of mitochondrial membrane potential, reduced oxygen consumption rate, and loss of ATP production. We identify several nuclear-encoded mitochondrial proteins, including polyadenylate binding protein-1 (PABPC1), which exhibit decreased abundance in mitochondria following treatment with HSP70 inhibitors. We also show that targeting HSP70 function leads to reduced levels of several mitochondrial-encoded RNA species that encode components of the electron transport chain. Our data indicate that small molecule inhibitors of HSP70 represent a new class of organelle proteostasis inhibitors that impair mitochondrial function in cancer cells, and therefore constitute novel therapeutics.
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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.