Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform

Abstract Tumor local invasion is the first step of metastasis cascade which remains the key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective invasion in a real time manner. Herein we aim...

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Autores principales:	Jiang-Long Xia, Wen-Jun Fan, Fei-Meng Zheng, Wen-Wen Zhang, Jia-Jun Xie, Meng-Ying Yang, Muhammad Kamran, Peng Wang, Hong-Ming Teng, Chun-Li Wang, Quentin Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a925e7f93d743c2904505bc2a19d2b5
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spelling	oai:doaj.org-article:2a925e7f93d743c2904505bc2a19d2b52021-12-02T16:06:15ZInhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform10.1038/s41598-017-02623-12045-2322https://doaj.org/article/2a925e7f93d743c2904505bc2a19d2b52017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02623-1https://doaj.org/toc/2045-2322Abstract Tumor local invasion is the first step of metastasis cascade which remains the key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective invasion in a real time manner. Herein we aim to develop a three-dimensional (3D) microfluidic cell invasion model to determine the dynamic process. In this model, collective invasion of breast cancer cells is induced by the concentration gradient of fetal bovine serum. We find that breast cancer cells adopt a collective movement rather than a random manner when the cells invade into extracellular matrix. The leading cells in the collective movement exhibit an increased expression of an Aurora kinase family protein - AURKA compared with the follower cells. Inhibition of AURKA kinase activity by VX680 or AKI603 significantly reduces the phosphorylation of ERK1/2 (Thr202/Tyr204) and collective cohort formation. Together, our study illustrates that AURKA acts as a potential therapeutic target for suppressing the process of tumor collective invasion. The 3D microfluidic cell invasion model is a reliable, measurable and dynamic platform for exploring potential drugs to inhibit tumor collective invasion.Jiang-Long XiaWen-Jun FanFei-Meng ZhengWen-Wen ZhangJia-Jun XieMeng-Ying YangMuhammad KamranPeng WangHong-Ming TengChun-Li WangQuentin LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiang-Long Xia Wen-Jun Fan Fei-Meng Zheng Wen-Wen Zhang Jia-Jun Xie Meng-Ying Yang Muhammad Kamran Peng Wang Hong-Ming Teng Chun-Li Wang Quentin Liu Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform
description	Abstract Tumor local invasion is the first step of metastasis cascade which remains the key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective invasion in a real time manner. Herein we aim to develop a three-dimensional (3D) microfluidic cell invasion model to determine the dynamic process. In this model, collective invasion of breast cancer cells is induced by the concentration gradient of fetal bovine serum. We find that breast cancer cells adopt a collective movement rather than a random manner when the cells invade into extracellular matrix. The leading cells in the collective movement exhibit an increased expression of an Aurora kinase family protein - AURKA compared with the follower cells. Inhibition of AURKA kinase activity by VX680 or AKI603 significantly reduces the phosphorylation of ERK1/2 (Thr202/Tyr204) and collective cohort formation. Together, our study illustrates that AURKA acts as a potential therapeutic target for suppressing the process of tumor collective invasion. The 3D microfluidic cell invasion model is a reliable, measurable and dynamic platform for exploring potential drugs to inhibit tumor collective invasion.
format	article
author	Jiang-Long Xia Wen-Jun Fan Fei-Meng Zheng Wen-Wen Zhang Jia-Jun Xie Meng-Ying Yang Muhammad Kamran Peng Wang Hong-Ming Teng Chun-Li Wang Quentin Liu
author_facet	Jiang-Long Xia Wen-Jun Fan Fei-Meng Zheng Wen-Wen Zhang Jia-Jun Xie Meng-Ying Yang Muhammad Kamran Peng Wang Hong-Ming Teng Chun-Li Wang Quentin Liu
author_sort	Jiang-Long Xia
title	Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform
title_short	Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform
title_full	Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform
title_fullStr	Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform
title_full_unstemmed	Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform
title_sort	inhibition of aurka kinase activity suppresses collective invasion in a microfluidic cell culture platform
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2a925e7f93d743c2904505bc2a19d2b5
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_version_	1718385012130185216

Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform

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