Plk1 overexpression induces chromosomal instability and suppresses tumor development

Cárcer, Guillermo de; Venkateswaran, Sharavan V.; Salgueiro, Lorena; Bakkali, Aicha El; Somogyi, Kálmán; Rowald, Konstantina; Montanes, Pablo; Sanclemente, Manuel; Escobar, Beatriz; Martino, Alba De; McGranahan, Nicholas; Malumbres, Marcos; Sotillo, Rocı́o

doi:10.1038/s41467-018-05429-5

Cited by 119 publications

(89 citation statements)

References 70 publications

(90 reference statements)

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“…Consistent with this idea, Plk1 overexpression has been found in numerous human tumours and seems to be involved in neoplastic transformation as well as in resistance to several chemotherapy drugs (Strebhardt and Ullrich 2006;Gutteridge et al 2016). Plk1-induced genome instability might also be detrimental though if too important, even to cancer cells, as recently reported (de Carcer et al 2018).…”

Section: Cell Survival and Genome Instability: Adaptation As A Doublesupporting

confidence: 60%

Adaptation in replicative senescence: a risky business

Coutelier

2019

Curr Genet

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Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. When the damage is not repaired, cells can, in some conditions, override the cell cycle arrest and proceed with proliferation, a phenomenon known as adaptation to DNA damage. A subpopulation of adapted cells might eventually survive, but only at the cost of extensive genome instability. How and in which context adaptation operates the trade-off between survival and genome stability is a fascinating question. After a brief review of the current knowledge on adaptation to DNA damage in budding yeast, we will discuss a new role of adaptation in the context of telomerase-negative cells and replicative senescence. We highlight the idea that, in all settings studied so far, survival through adaptation is a double-edged sword as it comes with increased genomic instability.

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Section: Cell Survival and Genome Instability: Adaptation As A Doublesupporting

confidence: 60%

Adaptation in replicative senescence: a risky business

Coutelier

2019

Curr Genet

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“…Polo-like kinase 1 (PLk1) as the highly conserved serine-threonine kinase has important functions in the cell mitosis and the genomic stability (Zhang et al 2007). PLK1 is regarded as the proto-oncogene and the attractive cancer target, which is overexpressed in various range of malignancies such as melanoma, prostate cancer and gastro-instestinal cancer (de Cárcer et al 2018;Bucur et al 2014). However, there is limited information on the functions of PLK1 for skin and feather follicles development.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Embryonic Skin Transcriptome in Anser cygnoides at Three Feather Follicles Developmental Stages

Liu

Sello

Sui

et al. 2020

G3 Genes|Genomes|Genetics

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In order to enrich the Anser cygnoides genome and identify the gene expression profiles of primary and secondary feather follicles development, de novo transcriptome assembly of skin tissues was established by analyzing three developmental stages at embryonic day 14, 18, and 28 (E14, E18, E28). Sequencing output generated 436,730,608 clean reads from nine libraries and de novo assembled into 56,301 unigenes. There were 2,298, 9,423 and 12,559 unigenes showing differential expression in three stages respectively. Furthermore, differentially expressed genes (DEGs) were functionally classified according to genes ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and series-cluster analysis. Relevant specific GO terms such as epithelium development, regulation of keratinocyte proliferation, morphogenesis of an epithelium were identified. In all, 15,144 DEGs were clustered into eight profiles with distinct expression patterns and 2,424 DEGs were assigned to 198 KEGG pathways. Skin development related pathways (mitogen-activated protein kinase signaling pathway, extra-cellular matrix -receptor interaction, Wingless-type signaling pathway) and genes (delta like canonical Notch ligand 1, fibroblast growth factor 2, Snail family transcriptional repressor 2, bone morphogenetic protein 6, polo like kinase 1) were identified, and eight DEGs were selected to verify the reliability of transcriptome results by real-time quantitative PCR. The findings of this study will provide the key insights into the complicated molecular mechanism and breeding techniques underlying the developmental characteristics of skin and feather follicles in Anser cygnoides.

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“…Of note, phosphorylation of AKT and S6K responded to AA stimulation in a delayed manner ( Figure 3A), probably as a secondary signaling event. Interestingly, treatment with AA activated PLK4 (phosphorylation at T170) 18 and PLK1 (phosphorylation at T210) 19 in the same time scale as did PDGFR ( Figure 3A). Importantly, while the PDGFR-selective inhibitor Crenol blocked AA-induced activation of PDGFR as well as MEK/ERK, JNK, AKT and S6K, validating the inhibitor functionality ( Figure 3B), this inhibitor also abrogated AA-stimulated activation of PLK4 and PLK1 ( Figure 3, C and D), placing them downstream of PDGFR signaling.…”

Section: Blocking Pdgfr Kinase Activity Abrogates Aa-stimulated Plk4 mentioning

confidence: 61%

A non-canonical role and regulations of polo-like kinase-4 in fibroblast cell-type transition

Urabe

Zhang

et al. 2019

Preprint

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Fibroblast-to-myofibroblast transition (FMT) is central to fibrosis. A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Whether this mitotic factor regulates cell type transitions was underexplored. Here we investigated PLK4's activation and expression and regulations thereof in platelet-derived growth factor (PDGF)induced FMT of rat aortic adventitial fibroblasts.PLK4 inhibition (with centrinone-B or siRNA) diminished not only PDGF AA-induced proliferation/migration, but also smooth muscle -actin and its transcription factor serum response factor's activity. While PDGFR inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and mRNA/protein expression, inhibition of p38 downstream of PDGFR had a similar effect. Further, the transcription of PLK4 (and PDGFR) was blocked by pan-inhibition of the bromo/extraterminal-domains chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect herein determined via siRNAs as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury.Thus, we identified a non-canonical role for PLK4 in FMT and its regulation by a BRD4/PDGFR-dominated pathway. This study implicates a potential PLK4-targeted antifibrotic intervention.

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Plk1 overexpression induces chromosomal instability and suppresses tumor development

Cited by 119 publications

References 70 publications

Adaptation in replicative senescence: a risky business

Adaptation in replicative senescence: a risky business

Characterization of Embryonic Skin Transcriptome in Anser cygnoides at Three Feather Follicles Developmental Stages

A non-canonical role and regulations of polo-like kinase-4 in fibroblast cell-type transition

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