Binucleated HeLa cells are formed by cytokinesis failure in starvation and keep the potential of proliferation

Nishimura, Kazunori; Watanabe, Soichi; Hayashida, Ryo; Sugishima, Setsuo; Iwasaka, Tsuyoshi; Kaku, Tsunehisa

doi:10.1007/s10616-015-9869-6

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…This indicated that STK16-IN-1 exerted its effect through STK16 kinase. We then screened a panel of mutations 16 in the STK16 kinase ATP binding pocket including the L98F, L98Q, G104 (N, D, E), and F100C and found that STK16 F100C mutation could significantly abolish STK16-IN-1's inhibitory effect (Supporting Figure 9). Transformation of this mutant into HeLa cells with a GFP-FLAG labeled STK16 kinase showed that the G2/M-phase cell cycle arrest effect of STK16-IN-1 was rescued (Figure 4E,F).…”

Section: Acs Chemical Biologymentioning

confidence: 99%

Discovery of a Highly Selective STK16 Kinase Inhibitor

et al. 2016

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STK16, a serine/threonine protein kinase, is ubiquitously expressed and is conserved among all eukaryotes. STK16 has been implicated to function in a variety of cellular processes such as VEGF and cargo secretion, but the pathways through which these effects are mediated remain to be elucidated. Through screening of our focused library of kinase inhibitors, we discovered a highly selective ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory activity against STK16 kinase (IC50: 0.295 μM) with excellent selectivity across the kinome as assessed using the KinomeScan profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with STK16-IN-1 results in a reduction in cell number and accumulation of binucleated cells, which can be recapitulated by RNAi knockdown of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight potentiation of the antiproliferative effects of the chemotherapeutics. STK16-IN-1 provides a useful tool compound for further elucidating the biological functions of STK16.

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Section: Acs Chemical Biologymentioning

confidence: 99%

Discovery of a Highly Selective STK16 Kinase Inhibitor

et al. 2016

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“…On the other hand, the number of binucleated cells in the progerin group is higher than that of the WT lamin A group, regardless of flow condition or shear level ( Figures 6E–G ). Binucleation appears to be a hallmark of progerin-expressing ECs, and shear-induced binucleation could be a result of cytokinesis failure in progerin-expressing ECs ( Nishimura et al, 2016 ). No significant changes were observed in WT lamin A-expressing cells under different flow conditions, indicating that normal shear stress did not prevent these cells from entering the G2/M phase.…”

Section: Resultsmentioning

confidence: 99%

Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells

Jiang

2022

Front. Aging

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Progerin as a mutated isoform of lamin A protein was first known to induce premature atherosclerosis progression in patients with Hutchinson-Gilford progeria syndrome (HGPS), and its role in provoking an inflammatory response in vascular cells and accelerating cell senescence has been investigated recently. However, how progerin triggers endothelial dysfunction that often occurs at the early stage of atherosclerosis in a mechanical environment has not been studied intensively. Here, we generated a stable endothelial cell line that expressed progerin and examined its effects on endothelial wound repair under laminar flow. We found decreased wound healing rate in progerin-expressing ECs under higher shear stress compared with those under low shear. Furthermore, the decreased wound recovery could be due to reduced number of cells at late mitosis, suggesting potential interference by progerin with endothelial proliferation. These findings provided insights into how progerin affects endothelial mechanotransduction and may contribute to the disruption of endothelial integrity in HGPS vasculature, as we continue to examine the mechanistic effect of progerin in shear-induced endothelial functions.

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“…We also found a higher average frequency of PNCs in participants with obesity, which is indicative of increased cytokinesis failure. Cancer cell lines have been used to demonstrate the mutagenic consequences of binucleated cells [ 96 ]. In a recent review, tetraploidy and cytokinesis failure have been evaluated as mechanisms for aneuploidy in subsequent mitotic cycles.…”

Section: Discussionmentioning

confidence: 99%

Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents

et al. 2021

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Background/objectives Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status. Subjects/methods We carried out a cross-sectional study with 132 participants, aged 10–18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2′-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay. Results As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability. Conclusions Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures.

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Binucleated HeLa cells are formed by cytokinesis failure in starvation and keep the potential of proliferation

Cited by 10 publications

References 24 publications

Discovery of a Highly Selective STK16 Kinase Inhibitor

Discovery of a Highly Selective STK16 Kinase Inhibitor

Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells

Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents

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