Inhibition of Aurora-A suppresses epithelial–mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells

Wan, Xiang; Long, Zi; Yan, Min; Xu, Jie; Xia, Liang; Liu, Li; Zhao, Yan; Huang, Xue F.; Wang, Xian Ren; Zhu, Xiao Feng; Hong, Ming; Liu, Quentin

doi:10.1093/carcin/bgn176

Cited by 90 publications

(105 citation statements)

References 45 publications

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“…Thus, the development of more EGFR-like biomarkers, which not only act as prognostic factors but also as therapeutic molecules, would lead to the improvement of individualized medicine for locally advanced NPC. Our present study showed that, as well as being a therapeutic target, (33,37) Aurora-A was an independent prognostic factor for OS, PFS, as well as DMFS (Tables 2,3).…”

Section: P-valuesupporting

confidence: 52%

“…Although we previous proved that Aurora-A might to be a novel therapeutic target for NPC, (33,37) its prognostic value had not been defined. Here, we randomly selected 69 IC/RT patients as the training set and 75 IC/CRT patients as the testing set, that had comparable clinical features (Table 1) and survival probability (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…(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%

“…(32) For esophageal squamous cell carcinoma cells, inhibition of Aurora-A suppressed tumor growth and sensitized the cells to docetaxel chemotherapy. (29) Moreover, our previous study showed that suppression of Aurora-A by VX-680 led to 46.0% tumor growth suppression, (33) suggesting Aurora-A might be a promising therapeutic molecular target for NPC and other types of HNSCC. However, the prognostic effect of Aurora-A has not been characterized in human NPC.…”

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confidence: 99%

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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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Section: P-valuesupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: P-valuementioning

confidence: 99%

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confidence: 99%

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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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“…This study raises the possibility that Aurora kinase signals through the MAPK signaling pathway. There have been some reports indicating crosstalk between AURKA and MAPK [5,6]. As for the relationship between AURKB and MAPK, Kanda et al [7] showed that AURKB kinase activity was involved in Ras-mediated cell transformation.…”

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confidence: 99%

AURKB and MAPK involvement in the regulation of the early stages of mouse zygote development

Lin

Tong

Feng³

et al. 2012

Sci. China Life Sci.

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Aurora kinases have become a hot topic for research as they have been found to play an important role in various stages of mitotic cell division and to participate in malignant conversions of tumors. The participation of Aurora kinases in the regulation of oocyte meiosis has been recently reported, but their participation in mammalian early embryonic development remained unclear. The object of our study was to establish the spatio-temporal expression pattern of Aurora kinase B (AURKB) in mouse zygotes during the first cleavage, to reveal its functions in the early development of mouse zygotes, and to define the involvement of AURKB in mitogen-activated protein kinase (MAPK) signaling. Our results showed that in mouse zygotes AURKB expression increased in G1 phase and peaked in M phase. AURKB protein distribution was found to be in association with nuclei and distributed throughout the cytoplasm in a cell cycle-dependent manner. Functional disruption of AURKB resulted in abnormal division phenotypes or mitotic impairments. U0126, a specific mitogen-activated protein kinase kinase (MEK) inhibitor, caused significantly altered morphologies of early embryos together with a decrease in protein expression and kinase activity of AURKB. Our results indicated that the activity of AURKB was required for regulating multiple stages of mitotic progression in the early development of mouse zygotes and was correlated with the activation of the MAPK pathway. AURKB, MAPK, mouse zygote, mitosis, cell cycle regulation Citation:Xu L, Liu T, Han F, et al. AURKB and MAPK involvement in the regulation of the early stages of mouse zygote development. Sci China Life Sci, 2012, 55: 47 -56,

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Aurora‐A Kinase: A Potent Oncogene and Target for Cancer Therapy

Yan

Wang

et al. 2016

Medicinal Research Reviews

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The Aurora kinase family comprises three serine/threonine kinases, Aurora-A, -B and -C. Among these, Aurora-A and -B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases have been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis.Aurora kinases therefore represent promising targets for anticancer therapeutics. So far, a number of Aurora kinase inhibitors (AKIs) have been generated, of which some are currently undergoing clinical trials. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in contributing tumorigenesis, the recent preclinical and clinical AKI data and potential alternative routes for Aurora-A kinase inhibition.Key words: Aurora-A; Aurora kinase inhibitors (AKIs); targeted cancer therapy; mitosis; tumorigenesis 3 In mammals, the Aurora family of serine/threonine kinases consists of Aurora-A, -B and -C, which share a highly conserved catalytic domain containing auto-phosphorylating sites. The catalytic domain is flanked by a very short C-terminal tail and an N-terminal domain of variable lengths 1,2 . In the C-terminal regions of Auroras, there exists a short amino-acid peptide motif called "destruction box" (D-box). The D-box is recognized by the anaphase-promoting complex/cyclosome (APC/C) for degradation through the ubiquitin/proteasome-dependent pathway ( Fig. 1A). Despite their structural similarities, the expression patterns, cellular localization and physiological functions of these three Aurora kinases are largely distinct.Aurora-A and -B are commonly expressed in most cell types whereas Aurora-C is specially expressed in the testis. Both Aurora-A and -B play key roles in regulating cell-cycle progression from G2 through to cytokinesis. Aurora-C has a unique physiological role in spermatogenesis and functions as a chromosomal passenger protein similar to Aurora-B in mitosis 2 .Overexpression of Aurora-A and -B have been found in multiple types of cancer (Table 1), which function as oncogenes to promote tumorigenesis, providing potential targets for cancer therapy.However, comparatively little information is available regarding the roles of Aurora-C in cancer.In this review, we will focus on recent progress as well as the main unresolved issues associated with Aurora-A in cancer.4 1 FUNCTIONS OF AURORA-A In normal cells a. MitosisIn G1 phase, the level of Aurora-A is rarely detectable. During S phase, a small proportion of Aurora-A is first detected at centrosomes. At late G2 phase, Aurora-A accumulates evidently at centrosomes and becomes activated 3 . During prometaphase and metaphase, active Aurora-A localizes on bipolar spindles and spindle poles after...

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Inhibition of Aurora-A suppresses epithelial–mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells

Cited by 90 publications

References 45 publications

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

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

AURKB and MAPK involvement in the regulation of the early stages of mouse zygote development

Aurora‐A Kinase: A Potent Oncogene and Target for Cancer Therapy

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