ArticleThe EMBO journal2025
Proteogenomic analysis reveals adaptive strategies for alleviating the consequences of aneuploidy in cancer.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- 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
- Protein buffering of aneuploidy is driven by coordinated factors identified through machine learning.Molecular systems biology · 2026Article
- The IQ-compete assay for measuring mitochondrial protein import efficiencies in living yeast cells.FEBS letters · 2026Article
- Modeling and targeting general and chromosome-specific aneuploidy in cancer.Genes & development · 2025Review
- The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025Review
- Article
- Carcinogenesis trajectories.Frontiers in cell and developmental biology · 2025Article
- Reduction of chromosomal instability and inflammation is a common aspect of adaptation to aneuploidy.EMBO reports · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Aneuploidy is prevalent in cancer and associates with fitness advantage and poor patient prognosis. Yet, experimentally induced aneuploidy initially leads to adverse effects and impaired proliferation, suggesting that cancer cells must adapt to aneuploidy. We performed in vitro evolution of cells with extra chromosomes and obtained cell lines with improved proliferation and gene expression changes congruent with changes in aneuploid cancers. Integrated analysis of cancer multi-omics data and model cells revealed increased expression of DNA replicative and repair factors, reduced genomic instability, and reduced lysosomal degradation. We identified E2F4 and FOXM1 as transcription factors strongly associated with adaptation to aneuploidy in vitro and in cancers and validated this finding. The adaptation to aneuploidy also coincided with specific copy number aberrations that correlate with poor patient prognosis. Chromosomal engineering mimicking these aberrations improved aneuploid cell proliferation, while loss of previously present extra chromosomes impaired it. The identified common adaptation strategies suggest replication stress, genomic instability, and lysosomal stress as common liabilities of aneuploid cancers.
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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.