ArticleJournal of cell science2018
Compensatory increases of select proteostasis networks after Hsp70 inhibition in cancer cells.
Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Review
- When "loss-of-function" means proteostasis burden: Thinking again about coding DNA variants.American journal of human genetics · 2025Article
- 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
- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
- Non-Essential Amino Acid Availability Influences Proteostasis and Breast Cancer Cell Survival During Proteotoxic Stress.Molecular cancer research : MCR · 2023Article
- Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics.Genes & diseases · 2023Review
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.International journal of molecular sciences · 2023Review
- Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells.Journal of medicinal chemistry · 2021Article
- Synthesis and evaluation of bifunctional PTP4A3 phosphatase inhibitors activating the ER stress pathway.Bioorganic & medicinal chemistry letters · 2021Article
- Article
- Proteotoxic Stress and Cell Death in Cancer Cells.Cancers · 2020Review
- Hsp70 and the Unfolded Protein Response as a Challenging Drug Target and an Inspiration for Probe Molecule Development.ACS medicinal chemistry letters · 2020Article
- Molecular Chaperones: A Double-Edged Sword in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2020Review
- Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells thrive when challenged with proteotoxic stress by inducing components of the protein folding, proteasome, autophagy and unfolded protein response (UPR) pathways. Consequently, specific molecular chaperones have been validated as targets for anti-cancer therapies. For example, inhibition of Hsp70 family proteins (hereafter Hsp70) in rhabdomyosarcoma triggers UPR induction and apoptosis. To define how these cancer cells respond to compromised proteostasis, we compared rhabdomyosarcoma cells that were sensitive (RMS13) or resistant (RMS13-R) to the Hsp70 inhibitor MAL3-101. We discovered that endoplasmic reticulum-associated degradation (ERAD) and autophagy were activated in RMS13-R cells, suggesting that resistant cells overcome Hsp70 ablation by increasing misfolded protein degradation. Indeed, RMS13-R cells degraded ERAD substrates more rapidly than RMS cells and induced the autophagy pathway. Surprisingly, inhibition of the proteasome or ERAD had no effect on RMS13-R cell survival, but silencing of select autophagy components or treatment with autophagy inhibitors restored MAL3-101 sensitivity and led to apoptosis. These data indicate a route through which cancer cells overcome a chaperone-based therapy, define how cells can adapt to Hsp70 inhibition, and demonstrate the value of combined chaperone and autophagy-based therapies.This article has an associated First Person interview with the first author of the paper.
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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.