ArticleNature communications2024
Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Biosynthesis of silver and gold nanoparticles usingBiomedical reports · 2026Article
- Pretreatment Chromosomal Instability Correlates With Radiation Sensitivity in Squamous Cell Cancers.International journal of radiation oncology, biology, physics · 2026Article
- 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
- PARP1 Suppression Drives ROS Resistance in Aneuploid Cancer Cells.bioRxiv : the preprint server for biology · 2026Article
- p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism.Nature genetics · 2026Article
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Unscheduled polyploidy synergizes with oncogenic mutations to enhance genome instability and tumorigenesis.Cancer letters · 2025Article
- Origin of chromosome 12 trisomy surge in human induced pluripotent stem cells.The Journal of cell biology · 2025Article
- Modeling and targeting general and chromosome-specific aneuploidy in cancer.Genes & development · 2025Review
- Depletion of aneuploid cells is shaped by cell-to-cell interactions.Cell genomics · 2025Article
- Article
- Aneuploidy generates enhanced nucleotide dependency and sensitivity to metabolic perturbation.Genes & development · 2025Article
- A Positive Feedback DNA-PK/MYT1L-CXCR1-ERK1/2 Proliferative Signaling Loop in Glioblastoma.International journal of molecular sciences · 2025Article
- Proteogenomic analysis reveals adaptive strategies for alleviating the consequences of aneuploidy in cancer.The EMBO journal · 2025Article
- A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.Nature communications · 2025Article
Corrections and comments
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Authors and funding
29 authors.
Funding
Abstract
Aneuploidy is a hallmark of human cancer, yet the molecular mechanisms to cope with aneuploidy-induced cellular stresses remain largely unknown. Here, we induce chromosome mis-segregation in non-transformed RPE1-hTERT cells and derive multiple stable clones with various degrees of aneuploidy. We perform a systematic genomic, transcriptomic and proteomic profiling of 6 isogenic clones, using whole-exome DNA, mRNA and miRNA sequencing, as well as proteomics. Concomitantly, we functionally interrogate their cellular vulnerabilities, using genome-wide CRISPR/Cas9 and large-scale drug screens. Aneuploid clones activate the DNA damage response and are more resistant to further DNA damage induction. Aneuploid cells also exhibit elevated RAF/MEK/ERK pathway activity and are more sensitive to clinically-relevant drugs targeting this pathway, and in particular to CRAF inhibition. Importantly, CRAF and MEK inhibition sensitize aneuploid cells to DNA damage-inducing chemotherapies and to PARP inhibitors. We validate these results in human cancer cell lines. Moreover, resistance of cancer patients to olaparib is associated with high levels of RAF/MEK/ERK signaling, specifically in highly-aneuploid tumors. Overall, our study provides a comprehensive resource for genetically-matched karyotypically-stable cells of various aneuploidy states, and reveals a therapeutically-relevant cellular dependency of aneuploid cells.
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