ArticleCancer discovery2024
Increased RNA and Protein Degradation Is Required for Counteracting Transcriptional Burden and Proteotoxic Stress in Human Aneuploid Cells.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Article
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cell and Nuclear Size Is Associated with Chromosomal Instability and Tumorigenicity in Cancer Cells That Undergo Whole Genome Doubling.Cancer research · 2026Article
- Combinatorial effects of multiple genes contribute to beneficial aneuploidy phenotypes.EMBO reports · 2026Article
- Paired CRISPR screens identify mitochondrial metabolism and UBE2H as aneuploid-specific dependencies in human cancer cell lines.bioRxiv : the preprint server for biology · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Impact of Chromosomal Instability and Aneuploidy in Cancer Development.Annual review of cancer biology · 2026Article
- Protein buffering of aneuploidy is driven by coordinated factors identified through machine learning.Molecular systems biology · 2026Article
- From stress to strength: mechanotransducing poly(aneu)ploidy into a community-level advantage in cancer.Cancer metastasis reviews · 2026Review
- Pharmacological perturbation of splicing elicits SMG1 reduction: Implications for cancer therapy.iScience · 2026Article
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- Investigating the Consequences of Aneuploidy in Cancer and Normal Tissue.Advances in experimental medicine and biology · 2026Review
- BMDx2: A Tool for Integrating Toxicogenomics-Based Dose-Dependency Analysis and AOP-Based Mechanistic Insights.Small methods · 2025Article
- NovumRNA: Accurate prediction of non-canonical tumor antigens from RNA sequencing data.iScience · 2025Article
- Modeling and targeting general and chromosome-specific aneuploidy in cancer.Genes & development · 2025Review
- CommensalAnnual review of microbiology · 2025Review
- LTO1 and YAE1 regulate MHC-I expression via nonsense-mediated RNA decay in tumor cells.Journal for immunotherapy of cancer · 2025Article
- Depletion of aneuploid cells is shaped by cell-to-cell interactions.Cell genomics · 2025Article
- The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025Review
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Abstract
Aneuploidy results in a stoichiometric imbalance of protein complexes that jeopardizes cellular fitness. Aneuploid cells thus need to compensate for the imbalanced DNA levels by regulating their RNA and protein levels, but the underlying molecular mechanisms remain unknown. In this study, we dissected multiple diploid versus aneuploid cell models. We found that aneuploid cells cope with transcriptional burden by increasing several RNA degradation pathways, and are consequently more sensitive to the perturbation of RNA degradation. At the protein level, aneuploid cells mitigate proteotoxic stress by reducing protein translation and increasing protein degradation, rendering them more sensitive to proteasome inhibition. These findings were recapitulated across hundreds of human cancer cell lines and primary tumors, and aneuploidy levels were significantly associated with the response of patients with multiple myeloma to proteasome inhibitors. Aneuploid cells are therefore preferentially dependent on several key nodes along the gene expression process, creating clinically actionable vulnerabilities in aneuploid cells. Significance: Aneuploidy is a hallmark of cancer that is associated with poor prognosis and worse drug response. We reveal that cells with extra chromosomes compensate for their imbalanced DNA content by altering their RNA and protein metabolism, rendering them more sensitive to perturbation of RNA and protein degradation. See related commentary by Bakhoum, p. 2315.
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