Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer

NCUIR > college of Health Sciences and Technology > Department of Biomedical Sciences and Engineering > journal & Dissertation > Item 987654321/103005

Please use this identifier to cite or link to this item: https://ir.lib.ncu.edu.tw/handle/987654321/103005

Title:	Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
Authors:	蘇立仁;Chen, Chang-Han;Chang, Alice YW;Li, Shau-Hsuan;Tsai, Hsin-Ting;Shiu, Li-Yen;Su, Li-Jen;Wang, Wen-Lung;Chiu, Tai-Jen;Luo, Sheng-Dean;Huang, Tai-Lin;Chien, Chih-Yen
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Analysis;Aurora Kinase A - genetics;Biomedical and Life Sciences;Biomedicine;Cancer Research;Care and treatment;Cell Cycle Proteins - genetics;Cell Line, Tumor;Cell Movement - genetics;Cell Proliferation - genetics;Cell Survival - genetics;Development and progression;Diagnosis;Gene expression;Gene Expression Regulation, Neoplastic - genetics;Head and Neck Neoplasms - genetics;Humans;Immunohistochemistry;Matrix Metalloproteinases - genetics;Medical research;Medicine, Experimental;Metastasis;Neoplasm Invasiveness - genetics;Nuclear Proteins - genetics;Oncology;Phosphatidylinositol 3-Kinases - genetics;RNA, Messenger - genetics;Signal Transduction - genetics
Date:	2015-04-12
Issue Date:	2026-04-23 11:21:43 (UTC+8)
Publisher:	BioMed Central Ltd.;London: BioMed Central
Abstract:	摘要： Background Head and neck cancer (HNC) is a highly invasive cancer. Aurora-A has been reported for a number of malignancies. However, the identity of downstream effectors responsible for its aggressive phenotype in HNC remains underinvestigated. Methods The mRNA and protein expression levels of Aurora-A and FLJ10540 were assessed in HNC specimens and cell lines using RT-qPCR, western blot, Oncomine, and microarray database analysis. The downstream molecular mechanisms of Aurora-A were confirmed by RT-qPCR, western blot, luciferase reporter, confocal microscopy analyses, immunoprecipitation, colony formation, cell viability, and xenograft model. Cellular functions in response to Aurora-A-modulated downstream targets such as FLJ10540 and MMPs were examined in vitro and in vivo , including cell growth, motility and chemosensitivity. Aurora-A/FLJ10540/MMPs expression was determined in cancer and adjacent normal tissues from HNC patients by immunohistochemistry approach. Results In the current study, Aurora-A exhibited similar gene expression profiles with FLJ10540 by using accessibly public microarray and Oncomine database analysis, raising the possibility that these molecules might coordinately participate in cancer progression and metastasis of HNC. These two molecules connection were also examined in cell lines and tissues of HNC. Aurora-A overexpression could not only bind to the promoter of FLJ10540 to induce FLJ10540 expression, but also increase both mRNA and protein levels of MMP-7 and MMP-10 in HNC cells. Conversely, depletion of Aurora-A expression by using siRNA or Aurora-A kinase inhibitor, MLN8237, suppressed FLJ10540, MMP-7 and MMP-10 mRNA and protein expressions in vitro and in vivo . In addition, the FLJ10540-PI3K complex was destroyed by inhibition the Aurora-A kinase activity. Forced overexpression of FLJ10540 in Aurora-A-depleted or in MLN8237-treated HNC cells attenuated the effect on cytotoxicity to cisplatin. Elevated Aurora-A expression in HNC cells led to the characteristics of more aggressive malignancy, including enhanced chemoresistance and increased the abilities of proliferation, migration and invasion, which was required for FLJ10540/MMP-7 or FLJ10540/MMP-10 expressions. Finally, immunohistochemical analysis of human HNC specimens showed a significant positively correlation among Aurora-A, FLJ10540, MMP-7 and MMP-10 expressions. Conclusion Together, our findings define a novel mechanism by which Aurora-A promotes cell malignancy, with potential implications for understanding the clinical action of Aurora-A. 其他題名： Mol Cancer 出版者： London: BioMed Central 出版日期： 2015-04-12 出處： Molecular cancer, 2015-04, Vol.14 (1), p.83-83, Article 83 資源來源： Publicly Available Content Database 版權： Chen et al.; licensee BioMed Central. 2015 版權： COPYRIGHT 2015 BioMed Central Ltd. 識別號： ISSN: 1476-4598 識別號： EISSN: 1476-4598 識別號： DOI: 10.1186/s12943-015-0348-7 識別號： PMID: 25889801
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	17	View/Open

社群 sharing

Loading...