2021
DOI: 10.1158/0008-5472.can-20-1377
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PLK1 Induces Chromosomal Instability and Overrides Cell-Cycle Checkpoints to Drive Tumorigenesis

Abstract: Polo-like kinase 1 (PLK1) is an essential cell-cycle regulator that is frequently overexpressed in various human cancers. To determine whether Plk1 overexpression drives tumorigenesis, we established transgenic mouse lines that ubiquitously express increased levels of Plk1. High Plk1 levels were a driving force for different types of spontaneous tumors. Increased Plk1 levels resulted in multiple defects in mitosis and cytokinesis, supernumerary centrosomes, and compromised cell-cycle checkpoints, allowing accu… Show more

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Cited by 53 publications
(54 citation statements)
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“…PLK1, a member of the serine/threonine-protein kinase family, is a key regulator of nonmitotic processes and phenomena, such as DNA replication, DDR and G2 DNA damage checkpoint recovery, chromosome dynamics, and microtubule dynamics, and it is activated by phosphorylation at the G2/M phase boundary [ 15 ]. A study by Lilia Gheghiani provides in vivo proof that abnormal expression of PLK1 triggers the overriding of cell cycle checkpoints to drive tumorigenesis and chromosomal instability and that high expression levels of PLK1 are always correlated with poorer patient prognosis and are related to high tumour grade, which strongly indicates that PLK1 plays key roles in tumour progression and initiation [ 12 , 16 , 17 ]. Furthermore, PLK1 activity is inhibited by ATM/ATR-dependent checkpoint pathways during the DDR, and phosphorylation of PLK1 at T210, the major activation site of PLK1, is a potential target of DNA damage checkpoints [ 18 ].…”
Section: Discussionmentioning
confidence: 99%
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“…PLK1, a member of the serine/threonine-protein kinase family, is a key regulator of nonmitotic processes and phenomena, such as DNA replication, DDR and G2 DNA damage checkpoint recovery, chromosome dynamics, and microtubule dynamics, and it is activated by phosphorylation at the G2/M phase boundary [ 15 ]. A study by Lilia Gheghiani provides in vivo proof that abnormal expression of PLK1 triggers the overriding of cell cycle checkpoints to drive tumorigenesis and chromosomal instability and that high expression levels of PLK1 are always correlated with poorer patient prognosis and are related to high tumour grade, which strongly indicates that PLK1 plays key roles in tumour progression and initiation [ 12 , 16 , 17 ]. Furthermore, PLK1 activity is inhibited by ATM/ATR-dependent checkpoint pathways during the DDR, and phosphorylation of PLK1 at T210, the major activation site of PLK1, is a potential target of DNA damage checkpoints [ 18 ].…”
Section: Discussionmentioning
confidence: 99%
“…Polo-like kinase 1 (PLK1), an essential cell cycle regulator and a member of the serine/threonine-protein kinase family, is overexpressed in various human cancers. A novel study provided in vivo evidence that PLK1 induces chromosomal instability and overrides cell cycle checkpoints to drive tumorigenesis [ 12 ]. In another study, it was reported that RO3280 (a PLK1 inhibitor) restrained the proliferation of cancer cells by inducing cell cycle arrest at the G2/M point [ 13 ].…”
Section: Introductionmentioning
confidence: 99%
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“…To evaluate tumor growth, tumor size (V) was measured every 3 days by using digital calipers and recorded as volumes (mm 3 ) that were calculated according to the formula: V=0.5 × length (L) × width (W) 2 . All the animals were euthanized when the neoplastic lesions exceeded 1000 mm 3 .…”
Section: Mice and Model Animal Experimentsmentioning
confidence: 99%
“…PLK1, a member of polo-like kinase (PLK) family, serves to control the checkpoint of cell division, a process indispensable in complete mitosis [1]. PLK1 has been found to be over-expressed in multiple cancers, including NSCLC, and the upregulated PLK1 is indicative of an unfavorable prognosis [2][3][4]. Furthermore, some studies showed that PLK1 expression level could be a reliable measure of risk for metastasis [5,6].…”
Section: Introductionmentioning
confidence: 99%