ArticleProceedings of the National Academy of Sciences of the United States of America2010
Plk4 is required for cytokinesis and maintenance of chromosomal stability.
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 70 papers.
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Who cites it
70 citing papers in PubMed, 106 citations in OpenAlex.
- Skeletal muscle dedifferentiation requires centrosomes.NPJ Regenerative medicine · 2026Article
- Critical constituents and assembly principles of centriole biogenesis in human cells.Nature reviews. Molecular cell biology · 2026Review
- Review
- Role of PLK4 inhibition in cancer therapy.Cancer metastasis reviews · 2025Review
- Amplified centrosomes-more than just a threat.EMBO reports · 2024Review
- STIL overexpression shortens lifespan and reduces tumor formation in mice.PLoS genetics · 2024Article
- Spermatocytes have the capacity to segregate chromosomes despite centriole duplication failure.EMBO reports · 2024Article
- CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.Nature communications · 2024Article
- CRL4Life science alliance · 2024Article
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
- Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer.International journal of biological sciences · 2023Article
- Transmission ratio distortion of mutations in the master regulator of centriole biogenesis PLK4.Human genetics · 2022Article
- Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer.Journal of pathology and translational medicine · 2022Article
- Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signaling pathway in bladder cancer.FEBS open bio · 2021Article
- Centriole and Golgi microtubule nucleation are dispensable for the migration of human neutrophil-like cells.Molecular biology of the cell · 2021Article
- Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Review
- Role of Polo-Like Kinase 4 (PLK4) in Epithelial Cancers and Recent Progress in its Small Molecule Targeting for Cancer Management.Molecular cancer therapeutics · 2021Review
- Aneuploidy as a promoter and suppressor of malignant growth.Nature reviews. Cancer · 2021Review
- Polo-Like Kinase 4's Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy.Frontiers in oncology · 2021Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Aneuploidy is a characteristic feature of established cancers and can promote tumor development. Aneuploidy may arise directly, through unequal distribution of chromosomes into daughter cells, or indirectly, through a tetraploid intermediate. The polo family kinase Plk4/Sak is required for late mitotic progression and is haploinsufficient for tumor suppression in mice. Here we show that loss of heterozygosity (LOH) occurs at the Plk4 locus in 50% of human hepatocellular carcinomas (HCC) and is present even in preneoplastic cirrhotic liver nodules. LOH at Plk4 is associated with reduced Plk4 expression in HCC tumors but not with mutations in the remaining allele. Plk4(+/-) murine embryonic fibroblasts (MEFs) at early passage show a high incidence of multinucleation, supernumerary centrosomes, and a near-tetraploid karyotype. Underlying these phenotypes is a high rate of primary cytokinesis failure, associated with aberrant actomyosin ring formation, reduced RhoA activation, and failure to localize the RhoA guanine nucleotide exchange factor Ect2 to the spindle midbody. We further show that Plk4 normally localizes to the midbody and binds to and phosphorylates Ect2 in vitro. With serial passaging Plk4(+/-) MEFs rapidly immortalize, acquiring an increasing burden of nonclonal and clonal gross chromosomal irregularities, and form tumors in vivo. Our results indicate that haploid levels of Plk4 disrupt RhoGTPase function during cytokinesis, resulting in aneuploidy and tumorigenesis, thus implicating early LOH at Plk4 as one of the drivers of human hepatocellular carcinogenesis. These findings represent an advance in our understanding of genetic predisposition to HCC, which continues to increase in incidence globally and particularly in North America.
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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.