ArticleMolecular cancer therapeutics2009
Oncogenic transformation confers a selective susceptibility to the combined suppression of the proteasome and autophagy.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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Who cites it
63 citing papers in PubMed, 110 citations in OpenAlex.
- Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors.The Journal of clinical investigation · 2013Trial
- Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases.Nature reviews. Molecular cell biology · 2024Review
- Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.Discover oncology · 2024Review
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- Therapeutic potential of autophagy activators and inhibitors in lung and breast cancer- a review.Molecular biology reports · 2022Review
- Identification and validation of selective deubiquitinase inhibitors.Cell chemical biology · 2021Article
- Liver-specific deletion of mechanistic target of rapamycin does not protect against acetaminophen-induced liver injury in mice.Liver research (Beijing, China) · 2021Article
- Autophagy and liver cancer.Clinical and molecular hepatology · 2020Review
- Bortezomib Treatment Modulates Autophagy in Multiple Myeloma.Journal of clinical medicine · 2020Article
- Chlorpromazine protects against acetaminophen-induced liver injury in mice by modulating autophagy and c-Jun N-terminal kinase activation.Liver research (Beijing, China) · 2019Article
- Chloroquine and nanoparticle drug delivery: A promising combination.Pharmacology & therapeutics · 2018Review
- Impaired Fasting-Induced Adaptive Lipid Droplet Biogenesis in Liver-Specific Atg5-Deficient Mouse Liver Is Mediated by Persistent Nuclear Factor-Like 2 Activation.The American journal of pathology · 2018Article
- Rapid induction of p62 and GABARAPL1 upon proteasome inhibition promotes survival before autophagy activation.The Journal of cell biology · 2018Article
- Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy.Oxidative medicine and cellular longevity · 2018Review
- Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing.Cancer metastasis reviews · 2017Article
- Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging.International journal of molecular sciences · 2017Review
- Proteasome inhibitors in glioblastoma.Oncology letters · 2017Article
- Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents.Ecancermedicalscience · 2017Article
- Autophagy, Endoplasmic Reticulum Stress and the Unfolded Protein Response in Intracerebral Hemorrhage.Translational neuroscience · 2017Article
- Nrf2 but not autophagy inhibition is associated with the survival of wild-type epidermal growth factor receptor non-small cell lung cancer cells.Toxicology and applied pharmacology · 2016Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The proteasome and the autophagy systems are two evolutionarily conserved mechanisms for degrading intracellular materials. They are functionally coupled and suppression of the proteasome promotes autophagy. Although suppression of the proteasome leads to cell death, suppression of autophagy can be either prodeath or prosurvival. To understand the underlining mechanism of this dichotomy and its potential clinical implications, we treated various transformed and nontransformed human cells with proteasome inhibitors. We found that whether autophagy served a prosurvival role in this scenario was contingent on the cellular oncogenic status. Thus, autophagy suppression enhanced apoptosis induced by proteasome inhibitors in transformed cells, but not in nontransformed cells. Oncogenic transformation enhanced the ability of cells to initiate autophagy in response to stress, reflecting a stronger dependence of transformed cells on autophagy for survival. Indeed, a combined use of bortezomib, the only Food and Drug Administration-approved proteasome inhibitor for clinical use, and chloroquine, which inhibits autophagy by disturbing lysosomal functions, suppressed tumor growth more significantly than either agent alone in a xenograft model. These findings indicate that suppression of both intracellular degradation systems could constitute a novel strategy for enhanced cancer control in a tumor-specific way.
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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.