ArticleProceedings of the National Academy of Sciences of the United States of America2010
High-throughput screens in diploid cells identify factors that contribute to the acquisition of chromosomal instability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Simultaneous quantification of rDNA methylation and copy number: Constraints to natural variation in humans and cell lines.PloS one · 2025Article
- Acute exposure to dihydroxyacetone promotes genotoxicity and chromosomal instability in lung, cardiac, and liver cell models.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Impairment of α-tubulin and F-actin interactions of GJB3 induces aneuploidy in urothelial cells and promotes bladder cancer cell invasion.Cellular & molecular biology letters · 2024Article
- Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics.Cellular and molecular life sciences : CMLS · 2023Article
- Aneuploidy-inducing gene knockdowns overlap with cancer mutations and identify Orp3 as a B-cell lymphoma suppressor.Oncogene · 2020Article
- Inhibition of neddylation induces mitotic defects and alters MKLP1 accumulation at the midbody during cytokinesis.Cell cycle (Georgetown, Tex.) · 2019Article
- The diverse consequences of aneuploidy.Nature cell biology · 2019Review
- Extra View: Sirt1 Acts As A Gatekeeper Of Replication Initiation To Preserve Genomic Stability.Nucleus (Austin, Tex.) · 2018Review
- Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion.The EMBO journal · 2015Article
- Functional genomics identifies a requirement of pre-mRNA splicing factors for sister chromatid cohesion.The EMBO journal · 2014Article
- Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Mitotic errors, aneuploidy and micronuclei in Hodgkin lymphoma pathogenesis.Communicative & integrative biology · 2013Article
- The kelch protein KLHDC8B guards against mitotic errors, centrosomal amplification, and chromosomal instability.The Journal of biological chemistry · 2012Article
- WNK1 is required for mitosis and abscission.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chromosomal instability and the subsequent genetic mutations are considered to be critical factors in the development of the majority of solid tumors, but the mechanisms by which a stable diploid cell loses the ability to maintain genomic integrity are not well characterized. We have approached this critical issue through the use of high-throughput screens in untransformed diploid epithelial cells. In a screen of a cDNA library, we identified 13 kinases whose overexpression leads to increased ploidy. In a series of shRNA screens, we identified 16 kinases whose loss leads to increased ploidy. In both cDNA and shRNA screens, the majority of hits have not been linked previously to genomic stability. We further show that sustained loss of the shRNA screening hits leads to multipolar spindles and heterogeneous chromosome content, two characteristics of chromosomal instability. Loss of several of the kinases leads to loss of contact inhibition and to anchorage-independent growth, vital traits acquired during tumor development. We anticipate that this work will serve as a template for the comprehensive identification of pathways whose dysregulation can drive tumorigenesis through impaired karyotypic maintenance.
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