Assessment of Aurora a Kinase Expression in Breast Cancer: A Tool for Early Diagnosis?

Ferchichi, Imen; Hannachi, Samia; Baccar, A.; Triki, Raja Marrakchi; Cremet, Jean Yves; Romdhane, Khaled Ben; Prigent, Claude; Gaaied, Amel Ben Ammar El

doi:10.1155/2013/871929

Cited by 20 publications

(10 citation statements)

References 43 publications

(61 reference statements)

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“…Therefore AURKA plays an essential role in cell cycle. Overexpression and aberrant amplification of AURKA have been observed in several types of cancers, such as cancers of the breast, colon, ovary, and cutaneous melanoma 13 - 16 . Recent studies have shown that AURKA amplification and overexpression are associated with poor prognosis in diverse cancers 17 - 19 .…”

Section: Introductionmentioning

confidence: 99%

Increased AURKA Gene Copy Number Correlates with Poor Prognosis and Predicts the Efficacy of High-dose Interferon Therapy in Acral Melanoma

Yan¹,

Yu²,

Wu³

et al. 2018

J. Cancer

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Background: AURKA kinase is an essential serine/threonine kinase for mitosis and chromosome stability. The aberrant amplification and overexpression of AURKA are commonly observed in various types of cancer, including cutaneous melanoma. However, the status and the clinical significance of AURKA copy number (CN) in acral melanoma (AM) have not been fully elucidated.Methods: Four hundred and seventy-two AM samples were included in the study. AURKA CN was examined using the QuantiGenePlex DNA Assay. We analysed the relationship of AURKA CN to clinicopathological characteristics and survival of patients with AM.Results: In this study, AURKA copy gain (set as more than 2.0 copies) was detected in 24.6% (116/472) of the samples. We did not observe any obvious correlation between clinicopathological characteristics and AURKA copy gain of the patients. However, patients with AURKA copy gain had a significantly shorter overall survival time (OS) and progression-free survival time (PFS) than those with normal AURKA CN (OS: P = 0.022; PFS: P < 0.001). Furthermore, multivariate Cox regression analysis showed that AURKA copy gain was an independent poor prognostic factor for patients with AM undergoing adjuvant interferon therapy.Conclusions: This study suggested that AURKA copy gain is an adverse prognostic factor for AM. Furthermore, AURKA copy gain may be a useful biomarker to predict the outcome of interferon therapy in patients with AM.

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Section: Introductionmentioning

confidence: 99%

Increased AURKA Gene Copy Number Correlates with Poor Prognosis and Predicts the Efficacy of High-dose Interferon Therapy in Acral Melanoma

Yan¹,

Yu²,

Wu³

et al. 2018

J. Cancer

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“…Alisertib is a second-generation and highly selective small molecule inhibitor of AURKA. Because aberrant expression of AURKA has been described in a variety of cancers, including breast cancer (41)(42)(43)(44)(45), the potential antineoplastic activity of alisertib is currently under investigation in a several clinical trials in patients with Figure 14. Oxidative stress and alisertib promote down-regulation of AURKA, ciliogenesis, and premature senescence in primary human fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Failure to reabsorb the primary cilium induces cellular senescence

2018

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Aurora kinase A (AURKA) is necessary for proper primary cilium disassembly before mitosis. We found that depletion of caveolin‐1 expression promotes primary cilia formation through the proteasomal‐dependent degradation of aurora kinase A and induces premature senescence in human fibroblasts. Down‐regulation of intraflagellar transport‐88, a protein essential for ciliogenesis, inhibits premature senescence induced by the depletion of caveolin‐1. In support of these findings, we showed that alisertib, a pharmacological inhibitor of AURKA, causes primary cilia formation and cellular senescence by irreversibly arresting cell growth. Suppression of primary cilia formation limits cellular senescence induced by alisertib. The primary cilium must be disassembled to free its centriole to form the centrosome, a necessary structure for mitotic spindle assembly and cell division. We showed that the use of the centriole to form primary cilia blocks centrosome formation and mitotic spindle assembly and prevents the completion of mitosis in cells in which cellular senescence is caused by the inhibition of AURKA. We also found that AURKA is down‐regulated and primary cilia formation is enhanced when cellular senescence is promoted by other senescence‐inducing stimuli, such as oxidative stress and UV light. Thus, we propose that impaired AURKA function induces premature senescence by preventing reabsorption of the primary cilium, which inhibits centrosome and mitotic spindle formation and consequently prevents the completion of mitosis. Our study causally links the inability of the cell to disassemble the primary cilium, a microtubule‐based cellular organelle, to the development of premature senescence, a functionally and pathologically relevant cellular state.—Jeffries, E. P., Di Filippo, M., Galbiati, F. Failure to reabsorb the primary cilium induces cellular senescence. FASEB J. 33, 4866–4882 (2019). http://www.fasebj.org

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“…Aurora A has recently been ranked among the top individual genes in terms of their concordance index values with respect to gene expression and survival data in computational modelling of disease prognosis in breast cancer . There are indications of oncogenic transformation activity of Aurora A with shifts from cytoplasmic staining in non‐malignant adjacent breast tissue to both cytoplasmic and nuclear compartments in tumour tissue, suggesting an oncogenic role for nuclear accumulation . Activated phosphorylated Aurora A Thr288 has recently been associated with tamoxifen resistance in ER‐positive breast cancer by phosphorylation of ERα at positions Ser167 and Ser305, leading to shorter recurrence‐free survival .…”

Section: Discussionmentioning

confidence: 99%

Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers

Aradottir

Reynisdottir

Stefansson

et al. 2014

The Journal of Pathology CR

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Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment.

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Assessment of Aurora a Kinase Expression in Breast Cancer: A Tool for Early Diagnosis?

Cited by 20 publications

References 43 publications

Increased AURKA Gene Copy Number Correlates with Poor Prognosis and Predicts the Efficacy of High-dose Interferon Therapy in Acral Melanoma

Increased AURKA Gene Copy Number Correlates with Poor Prognosis and Predicts the Efficacy of High-dose Interferon Therapy in Acral Melanoma

Failure to reabsorb the primary cilium induces cellular senescence

Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers

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