Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis

Xu, Jie; Yue, Cai Feng; Zhou, Wei; Qian, Yuan; Zhang, Yan; Wang, Shao Wu; Liu, An Wen; Liu, Quentin

doi:10.1186/1479-5876-12-200

Cited by 57 publications

(52 citation statements)

References 45 publications

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“…All eligible studies were published between 2005 and 2014. All TNM Stages (I-IV) were considered in 18 studies (46.2%) (9,18,20,27,28,30,(34)(35)(36)(37)(38)40,43,44,50,55,56,58), non-metastatic solid tumors (including Stage I-III or localized disease, based solely on singlestage disease or mixture of tumor stages) were considered in 12 (30.8%) studies (22,29,31,33,39,41,42,46,48,51,53,54); metastatic solid tumors (Stage IV) patients were considered in four studies (10.2%) (23,45,49,57); disease stage was not available were considered in five studies (12.8%). Four studies analyzing AURKA mRNA expression used real-time reverse transcription PCR (RT-PCR) (20,34,35,45); one study analyzing AURKA gene amplification by fluorescence in situ hybridization (FISH) (54); the other one used immunohistochemical (IHC) staining and RT-PCR (47); and the remaining 33 studies applied a immunohistochemistry detection method (9,18,19,21-23,27-33, 36-44,46,48-53,55-58).…”

Section: Characteristics Of Identified Studiesmentioning

confidence: 99%

“…One or more oncologic outcome parameters were analyzed on multivariate analysis in 33 studies (9,(18)(19)(20)(21)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)58). A significant association between high AURKA expression and the poor prognosis of patients was reported in 71.4% of studies on OS (9,18,31,32,(34)(35)(36)(37)39,(42)(43)(44)(45)48,(50)(51)(52)(53)…”

Section: Characteristics Of Identified Studiesmentioning

confidence: 99%

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Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis

Zhang¹,

Li²,

Zhang³

et al. 2015

Japanese Journal of Clinical Oncology

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Objective: The prognostic significance of Aurora kinase A expression in cancer patients is currently under debate. Here, we conducted the first comprehensive meta-analysis of the prognostic relevance of Aurora kinase A associated with survival in solid tumors. Methods: Pubmed was searched for studies evaluating the Aurora kinase A expression and survival in solid tumors through 10 October 2014. The main outcome analyzed was overall survival and secondary outcomes were progression-free survival, disease-free survival and cancer-specific survival. Pooled hazard ratio and 95% confidence intervals were calculated to assess the association. Subgroup and sensitivity analyses were also conducted. Results: Thirty-nine eligible studies enrolling 5523 patients were identified. The high Aurora kinase A expression level was significantly associated with shorter overall survival (hazard ratio = 2.31; 95% confidence interval, 1.81-2.95). Further subgroup analyses showed that our results were stable irrespective of the disease sites, stages and methods of Aurora kinase A expression. The high Aurora kinase A expression level was also associated with progression-free survival (hazard ratio = 2.68; 95% confidence interval, 1.96-3.69), disease-free survival (hazard ratio = 1.91; 95% confidence interval, 1.45-2.51) and cancer-specific survival (hazard ratio = 2.13; 95% confidence interval, 1.38-3.29). Conclusions: Our present meta-analysis indicates that the Aurora kinase A is an effective prognosticator in solid tumors patients. Further studies are required to explore the clinical utility of Aurora kinase A in solid tumor.

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Section: Characteristics Of Identified Studiesmentioning

confidence: 99%

Section: Characteristics Of Identified Studiesmentioning

confidence: 99%

Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis

Zhang¹,

Li²,

Zhang³

et al. 2015

Japanese Journal of Clinical Oncology

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“…12 The inhibition of Aurora A kinase causes DNA damage and renders cancer cells more sensitive to radiation. [13][14][15][16][17] Cancer cells responds to DNA damage by initiating the DNA-damage response, which induces cell cycle delay, more prolonged growth arrests and apoptosis of the lethally damaged cells. Gamma-H2AX is involved in recruitment of DNA damage repair factors to sites of double-strand breaks (DSB).…”

Section: Introductionmentioning

confidence: 99%

The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer

Jin

Zhang

et al. 2016

Cancer Biology & Therapy

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VX680 is a potent and selective inhibitor that targets the Aurora kinase family. The p38 mitogen-activated protein kinase (MAPK) regulates a large number of cellular pathways and plays an important role in the regulation of cell survival and apoptosis. This study aimed to evaluate the effect of VX680 on cervical cancer cells and investigate whether the effects on apoptosis are enhanced by the ablation of p38 MAPK activation. The results suggested that VX680 inhibited the proliferation of cervical cancer cells by causing G2/M phase arrest and endoreduplication and that the apoptotic effect was attenuated by the activation of p38 MAPK. However, the addition of BIRB796, which is an important p38 MAPK inhibitor, effectively eliminated the expression of p-p38 and hence significantly enhanced the cell death induced by VX680 in vitro. Further study demonstrated that BIRB796 cooperated with VX680 to suppress cervical cancer cell growth in a mouse xenograft model. Taken together, our results demonstrated that VX680 induced cell cycle arrest and endoreduplication in human cervical cancer cells. Combined treatment with VX680 and BIRB796 synergistically inhibited tumor growth both in vitro and in vivo. Dual blockade of Aurora kinases and p38 MAPK is therefore a promising strategy for cervical cancer treatment.

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“…Recently, we found that Aurora kinase inhibitor ZM induced mitotic slippage and resistant polyploidy in acute myeloid leukemia cells [30]. We further found that pan-Aurora kinase (-A and -B) inhibitor ZM [31], but not Aurora A inhibitor MLN8237 [32, 33], induced polyploidy in breast cancer (for all online suppl. material, see www.karger.com/doi/10.1159/000480322, Fig.…”

Section: Resultsmentioning

confidence: 83%

CyclinG1 Amplification Enhances Aurora Kinase Inhibitor-Induced Polyploid Resistance and Inhibition of Bcl-2 Pathway Reverses the Resistance

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: CyclinG1 (CycG1) is frequently overexpressed in solid tumors and overexpression of CycG1 promotes cell survival upon paclitaxel exposure by inducing polyploidy. Whether and how CycG1 regulates polyploidization caused by small molecular targeted inhibitors remains unclear. Methods: Immunohistochemistry and immunoblotting were utilized to examine protein expression. Cell proliferation was measured by ATPlite assay, and cell cycle distribution and apoptosis were measured by flow cytometry and/or DNA fragmentation assays. Results: Overexpression of CycG1 in breast cancer cells caused apoptosis-resistant polyploidy upon treatment with Aurora kinase inhibitor, ZM447439 (ZM). Addition of ABT-263, a small-molecule BH3 mimetic, to ZM, produced a synergistic loss of cell viability with greater sustained tumor growth inhibition in breast cancer cell lines. Decrease of Mcl-1 and increase of NOXA caused by ZM treatment, were responsible for the synergy. Furthermore, CycG1 was highly expressed in Triple-Negative-Breast-Cancer patients treated with paclitaxel and was paralleled by decreased cell survival. Conclusion: CycG1 is a crucial factor in ZM-induced polyploidy resistance, and ABT-263/ZM combination hold therapeutic utility in the CycG1-amplified subset of breast cancer and CycG1, thus, is a promising target in breast cancer.

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Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis

Cited by 57 publications

References 45 publications

Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis

Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis

The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer

CyclinG1 Amplification Enhances Aurora Kinase Inhibitor-Induced Polyploid Resistance and Inhibition of Bcl-2 Pathway Reverses the Resistance

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