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

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 Aur...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403844/
https://www.ncbi.nlm.nih.gov/pubmed/25889801
http://dx.doi.org/10.1186/s12943-015-0348-7
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author 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
author_facet 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
author_sort Chen, Chang-Han
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0348-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-44038442015-04-21 Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer 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 Mol Cancer Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0348-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-12 /pmc/articles/PMC4403844/ /pubmed/25889801 http://dx.doi.org/10.1186/s12943-015-0348-7 Text en © Chen et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
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
Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
title Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
title_full Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
title_fullStr Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
title_full_unstemmed Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
title_short Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer
title_sort suppression of aurora-a-flj10540 signaling axis prohibits the malignant state of head and neck cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403844/
https://www.ncbi.nlm.nih.gov/pubmed/25889801
http://dx.doi.org/10.1186/s12943-015-0348-7
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