Aurora Kinase A Messenger RNA Overexpression Is Correlated with Tumor Progression and Shortened Survival in Head and Neck Squamous Cell Carcinoma

Reiter, Rudolf; Gais, Peter; Jütting, Uta; Steuer-Vogt, M. K.; Pickhard, Anja; Bink, Karin; Rauser, Sandra; Laßmann, Silke; Höfler, Heinz; Werner, Martin; Walch, Axel

doi:10.1158/1078-0432.ccr-05-1650

Cited by 180 publications

(146 citation statements)

References 37 publications

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“…7a). The same series of cancers were stained for AURKA, which has been also found upregulated in ESCCs and HNSCCs [45][46][47][48] . We confirmed the presence of abundant AURKA-positive cells in both types of cancers (Fig.…”

Section: Sa-2xpamentioning

confidence: 97%

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

et al. 2014

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NANOG is a pluripotency transcription factor in embryonic stem cells; however, its role in adult tissues remains largely unexplored. Here we show that mouse NANOG is selectively expressed in stratified epithelia, most notably in the oesophagus where the Nanog promoter is hypomethylated. Interestingly, inducible ubiquitous overexpression of NANOG in mice causes hyperplasia selectively in the oesophagus, in association with increased cell proliferation. NANOG transcriptionally activates the mitotic programme, including Aurora A kinase (Aurka), in stratified epithelia, and endogenous NANOG directly binds to the Aurka promoter in primary keratinocytes. Interestingly, overexpression of Nanog or Aurka in mice increased proliferation and aneuploidy in the oesophageal basal epithelium. Finally, inactivation of NANOG in cell lines from oesophageal or head and neck squamous cell carcinomas (ESCCs or HNSCCs, respectively) results in lower levels of AURKA and decreased proliferation, and NANOG and AURKA expression are positively correlated in HNSCCs. Together, these results indicate that NANOG has a lineage-restricted mitogenic function in stratified epithelia.

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Section: Sa-2xpamentioning

confidence: 97%

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

et al. 2014

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“…4 Thus, it is not unexpected that these kinases have been described to be related with chromosomal instability, agressive growth and poor outcome in leukemia and in various malignancies like breast, bladder, ovarian, pancreatic and colon cancer. 1,[5][6][7][8] This group of kinases consists of three highly related kinases, known as AURKA (alias STK6/STK15/AurA), AURKB (alias STK12/STK5/AurB) and AURKC (alias STK13/AurC) in mammals. AURKA and -B are expressed in the majority of normal cell types.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

Pohl

Azuma²,

Zhang

et al. 2010

Pharmacogenomics J

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Aurora kinases are conserved eukaryotic serine-threonine kinases, which serve as key regulators of mammalian mitosis. Several studies revealed a distinct correlation between inaccurate chromosome segregation, leading to chromosomal number instability, cancer progression and poor outcome. The aim of this study was to investigate the correlation of Aurora kinases A (AURKA) and B (AURKB) with overall survival (OS) by quantifying gene expression analysis and evaluation of single-nucleotide polymorphisms (SNPs) in human colorectal cancer samples and assessing the associations with clinicopathological features. We evaluated intratumoral gene expression levels and SNPs of AURKA and -B from 41 patients with metastatic colorectal cancer (mCRC). Patients with a high expression level of AURKB (41.28) lived significantly shorter (n ¼ 11, median OS ¼ 6.4 months, 95% confidence interval (CI): 3.0-14.5 months) compared with patients with a low expression level (p1.28) (n ¼ 30, median OS ¼ 18.4 months, 95% CI: 14.7-27.8 months, P ¼ 0.026, Wald's test). Patients harboring any G-allele in AURKB 885A4G showed a significantly decreased OS (P ¼ 0.05, log-rank test). We did not find any associations with clinicopathological variables and AURKA gene expression levels. Our results suggest a potential role for AURKB inhibition in patients with mCRC; thereby supporting its potential role as a target in mCRC.

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“…(19,20) In tumors, aberrant expression of Aurora-A was negatively correlated with tumor stage, and lymph node as well as distant metastasis. (30,33) Given its importance in tumor initiation and progression, targeting of Aurora-A might to be a novel therapeutic selection for cancer treatment. Combined with docetaxel, Aurora-A inhibition suppressed 44.0% tumor growth in esophageal squamous cell carcinoma.…”

Section: P-valuementioning

confidence: 99%

“…(25)(26)(27)(28)(29) Upregulation of Aurora-A mRNA, for example, was correlated with the occurrence of regional lymph node metastasis for HNSCC. (30,31) Conversely, inhibition of Aurora-A by its specific small molecule inhibitor VX-680 potently suppressed the laryngeal HepG2 cell AKT1/2 phosphorylation as well as migration capacity, and sensitized the cell to X-ray irradiation. (32) For esophageal squamous cell carcinoma cells, inhibition of Aurora-A suppressed tumor growth and sensitized the cells to docetaxel chemotherapy.…”

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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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Aurora Kinase A Messenger RNA Overexpression Is Correlated with Tumor Progression and Shortened Survival in Head and Neck Squamous Cell Carcinoma

Cited by 180 publications

References 37 publications

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

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

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