Overexpression of Active Aurora-C Kinase Results in Cell Transformation and Tumour Formation

Khan, Jabbar; Ezan, Frédéric; Cremet, Jean-Yves; Fautrel, Alain; Gilot, David; Lambert, Marine; Benaud, Christelle; Troadec, Marie‐Bérengère; Prigent, Claude

doi:10.1371/journal.pone.0026512

Cited by 59 publications

(56 citation statements)

References 49 publications

(71 reference statements)

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“…One possible mechanism is that AURKC or its unknown binding partner could negatively regulate the affinity of Eg5 for microtubules as AURKA and TPX2 have been shown to do (Balchand et al, 2015;Giet et al, 1999). Although it was surprising that AURKC colocalized with MTOCs, this localization is consistent with reports demonstrating localization of human AURKC at centrosomes in cancer cell lines (Khan et al, 2011;Tsou et al, 2011). Some cancer cell types contain multiple centrosomes.…”

Section: Discussionsupporting

confidence: 84%

“…In some cancer cell lines, AURKC localizes to centrosomes (Dutertre et al, 2005;Khan et al, 2011), and overexpression of AURKC can rescue multipolar spindle formation in RBBP4 and RBBP7-depleted oocytes (Balboula et al, , 2015. Because we know that haspin regulates AURKC chromosomal localization (Nguyen et al, 2014), we re-evaluated AURKC and haspin localization.…”

Section: Haspin Activity Is Required For Aurkc Localization At Mtocsmentioning

confidence: 99%

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Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

Balboula

Nguyen

Gentilello

et al. 2016

Journal of Cell Science

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Meiotic oocytes lack classic centrosomes and, therefore, bipolar spindle assembly depends on clustering of acentriolar microtubuleorganizing centers (MTOCs) into two poles. However, the molecular mechanism regulating MTOC assembly into two poles is not fully understood. The kinase haspin (also known as GSG2) is required to regulate Aurora kinase C (AURKC) localization at chromosomes during meiosis I. Here, we show that inhibition of haspin perturbed MTOC clustering into two poles and the stability of the clustered MTOCs. Furthermore, we show that AURKC localizes to MTOCs in mouse oocytes. Inhibition of haspin perturbed the localization of AURKC at MTOCs, and overexpression of AURKC rescued the MTOC-clustering defects in haspin-inhibited oocytes. Taken together, our data uncover a role for haspin as a regulator of bipolar spindle assembly by regulating AURKC function at acentriolar MTOCs in oocytes.

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Section: Discussionsupporting

confidence: 84%

Section: Haspin Activity Is Required For Aurkc Localization At Mtocsmentioning

confidence: 99%

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

Balboula

Nguyen

Gentilello

et al. 2016

Journal of Cell Science

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“…1)”, i.e., AURKA (Aurora‐A) ,42 AURKB (Aurora‐B) ,43 AURKC (Aurora‐C) ,44 BIRC5 ,45 BUB1 ,46 CDC20 ,47 NEK2 48 and SPC25 ,48 were quantitatively evaluated by RT‐PCR analysis and added to Table 6. Levels of mRNA expression for the AURKA , AURKB , BIRC5 , BUB1 , CDC20 , NEK2 and SPC25 genes in CIMP‐positive RCCs in the initial cohort ( n = 14) were significantly higher than in CIMP‐negative RCCs ( n = 74) ( p = 2.447 × 10 −4 , 7.803 × 10 −4 , 6.077 × 10 −4 , 5.250 × 10 −5 , 1.706 × 10 −4 , 2.922 × 10 −4 and 2.152 × 10 −2 , respectively, Mann‐Whitney U test, Fig.…”

Section: Resultsmentioning

confidence: 99%

Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas

Arai¹,

Gotoh²,

Tian³

et al. 2015

Intl Journal of Cancer

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CpG‐island methylator phenotype (CIMP)‐positive clear cell renal cell carcinomas (RCCs) are characterized by accumulation of DNA hypermethylation of CpG islands, clinicopathological aggressiveness and poor patient outcome. The aim of this study was to clarify the molecular pathways participating in CIMP‐positive renal carcinogenesis. Genome (whole‐exome and copy number), transcriptome and proteome (two‐dimensional image converted analysis of liquid chromatography‐mass spectrometry) analyses were performed using tissue specimens of 87 CIMP‐negative and 14 CIMP‐positive clear cell RCCs and corresponding specimens of non‐cancerous renal cortex. Genes encoding microtubule‐associated proteins, such as DNAH2, DNAH5, DNAH10, RP1 and HAUS8, showed a 10% or higher incidence of genetic aberrations (non‐synonymous single‐nucleotide mutations and insertions/deletions) in CIMP‐positive RCCs, whereas CIMP‐negative RCCs lacked distinct genetic characteristics. MetaCore pathway analysis of CIMP‐positive RCCs revealed that alterations of mRNA or protein expression were significantly accumulated in six pathways, all participating in the spindle checkpoint, including the “The metaphase checkpoint (p = 1.427 × 10−6),” “Role of Anaphase Promoting Complex in cell cycle regulation (p = 7.444 × 10−6)” and “Spindle assembly and chromosome separation (p = 9.260 × 10−6)” pathways. Quantitative RT‐PCR analysis revealed that mRNA expression levels for genes included in such pathways, i.e., AURKA, AURKB, BIRC5, BUB1, CDC20, NEK2 and SPC25, were significantly higher in CIMP‐positive than in CIMP‐negative RCCs. All CIMP‐positive RCCs showed overexpression of Aurora kinases, AURKA and AURKB, and this overexpression was mainly attributable to increased copy number. These data suggest that abnormalities of the spindle checkpoint pathway participate in CIMP‐positive renal carcinogenesis, and that AURKA and AURKB may be potential therapeutic targets in more aggressive CIMP‐positive RCCs.

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“…Mitotic Aurora-A kinase belongs to a serine/threonine kinase family comprising two other members, Aurora-B and Aurora-C. (16)(17)(18) We and others have found that Aurora-A is essential in proper timing of mitotic entry and formation of bipolar spindles. (19,20) Overexpression of Aurora-A caused aberrant centrosome amplification, multipolar spindle structure, and aneuploidy.…”

mentioning

confidence: 99%

Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

et al. 2012

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Previously, we and others showed that hypoxia-inducible factor-1a (HIF-1a) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1a in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1a expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1a. We found that Aurora-A and HIF-1a were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progressionfree survival (44.8% vs 79.8%, P = 0.004), and distant metastasisfree survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1a was detected (P = 0.037). Importantly, although HIF-1a did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1a co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1a refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy. (Cancer Sci 2012; 103: 1586-1594

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Overexpression of Active Aurora-C Kinase Results in Cell Transformation and Tumour Formation

Cited by 59 publications

References 49 publications

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas

Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

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