{"doi":"10.3390/cancers15010030","title":"Apoptosis as a Barrier against CIN and Aneuploidy","abstract":"<jats:p>Aneuploidy is the gain or loss of entire chromosomes, chromosome arms or fragments. Over 100 years ago, aneuploidy was described to be a feature of cancer and is now known to be present in 68–90% of malignancies. Aneuploidy promotes cancer growth, reduces therapy response and frequently worsens prognosis. Chromosomal instability (CIN) is recognized as the main cause of aneuploidy. CIN itself is a dynamic but stochastic process consisting of different DNA content-altering events. These can include impaired replication fidelity and insufficient clearance of DNA damage as well as chromosomal mis-segregation, micronuclei formation, chromothripsis or cytokinesis failure. All these events can disembogue in segmental, structural and numerical chromosome alterations. While low levels of CIN can foster malignant disease, high levels frequently trigger cell death, which supports the “aneuploidy paradox” that refers to the intrinsically negative impact of a highly aberrant karyotype on cellular fitness. Here, we review how the cellular response to CIN and aneuploidy can drive the clearance of karyotypically unstable cells through the induction of apoptosis. Furthermore, we discuss the different modes of p53 activation triggered in response to mitotic perturbations that can potentially trigger CIN and/or aneuploidy.</jats:p>","journal":"Cancers","year":2022,"id":600813,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1540381,"name":"Filip Gallob","orcid":null,"position":1,"is_corresponding":false},{"id":1540382,"name":"Patricia Rieder","orcid":null,"position":2,"is_corresponding":false},{"id":628282,"name":"Andreas Villunger","orcid":"0000-0001-8259-4153","position":3,"is_corresponding":false},{"id":1540380,"name":"Johannes Weiss","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Apoptosis as a Barrier against CIN and Aneuploidy","abstract":"<jats:p>Aneuploidy is the gain or loss of entire chromosomes, chromosome arms or fragments. Over 100 years ago, aneuploidy was described to be a feature of cancer and is now known to be present in 68–90% of malignancies. Aneuploidy promotes cancer growth, reduces therapy response and frequently worsens prognosis. Chromosomal instability (CIN) is recognized as the main cause of aneuploidy. CIN itself is a dynamic but stochastic process consisting of different DNA content-altering events. These can include impaired replication fidelity and insufficient clearance of DNA damage as well as chromosomal mis-segregation, micronuclei formation, chromothripsis or cytokinesis failure. All these events can disembogue in segmental, structural and numerical chromosome alterations. While low levels of CIN can foster malignant disease, high levels frequently trigger cell death, which supports the “aneuploidy paradox” that refers to the intrinsically negative impact of a highly aberrant karyotype on cellular fitness. Here, we review how the cellular response to CIN and aneuploidy can drive the clearance of karyotypically unstable cells through the induction of apoptosis. Furthermore, we discuss the different modes of p53 activation triggered in response to mitotic perturbations that can potentially trigger CIN and/or aneuploidy.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36612027","pmcid":"PMC9817872","openalex_id":"https://openalex.org/W4312070622","authors":[],"funders":[{"funder_name":"Austrian Academy of Sciences (OeAW)","grant_id":"P-29499","title":null},{"funder_name":"Austrian Academy of Sciences (OeAW)","grant_id":"PIR-3","title":null},{"funder_name":"Austrian Academy of Sciences (OeAW)","grant_id":"787171","title":"The PIDDosome in Centrosome and Ploidy-Surveillance"},{"funder_name":"Austrian Academy of Sciences","grant_id":"NA","title":null},{"funder_name":"Austrian Science Fund FWF","grant_id":"P29499","title":null}],"total_grants":5,"fwci":0.645,"citation_percentile":0.62065401,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2072-6694/15/1/30/pdf?version=1672307888","host_type":"journal"},{"url":"https://www.mdpi.com/2072-6694/15/1/30/pdf?version=1672307888","host_type":"publisher"},{"url":"https://www.mdpi.com/2072-6694/15/1/30/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cancers15010030","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36612027","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/cancers15010030","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9817872","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9817872","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9817872?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/cancers15010030","host_type":""}],"fields_of_study":["Microtubule and mitosis dynamics","Chromosomal and Genetic Variations","Endoplasmic Reticulum Stress and Disease","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Aneuploidy","Chromosome instability","Chromothripsis","Mitosis","Genome instability","Cytokinesis","Biology","Mitotic catastrophe","DNA damage","Chromosome segregation","Cancer research","Cancer","Micronucleus test","Chromosome","Cancer cell","Cell biology","Genetics","Cell","Cell division","Medicine","DNA","Gene","Internal medicine","Apoptosis","p53","BCL2 family","Spindle Assembly Checkpoint (Sac)","Chromosomal Instability (Cin)","Review"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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