The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells

Abstract Nek2 (NIMA‐related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dy...

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Autores principales:	Yainyrette Rivera-Rivera, Mihaela Marina, Shirley Jusino, Miyoung Lee, Jaleisha Vélez Velázquez, Camille Chardón-Colón, Geraldine Vargas, Jaya Padmanabhan, Srikumar P. Chellappan, Harold I. Saavedra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/349186be6236452795f3845aa7cf9050
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spelling	oai:doaj.org-article:349186be6236452795f3845aa7cf90502021-12-02T17:39:20ZThe Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells10.1038/s41598-021-88512-02045-2322https://doaj.org/article/349186be6236452795f3845aa7cf90502021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88512-0https://doaj.org/toc/2045-2322Abstract Nek2 (NIMA‐related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dysfunction, and chromosome instability (CIN). Our group and others have suggested that Nek2 maintains high levels of CA/CIN, tumor growth, and drug resistance. We identified that Nek2 overexpression correlates with poor survival of breast cancer. However, the mechanisms driving these phenotypes are unknown. We now report that overexpression of Nek2 in MCF10A cells drives CA/CIN and aneuploidy. Besides, enhanced levels of Nek2 results in larger 3D acinar structures, but could not initiate tumors in a p53+/+ or a p53−/− xenograft model. Nek2 overexpression induced the epithelial-to-mesenchymal transition (EMT) while its downregulation reduced the expression of the mesenchymal marker vimentin. Furthermore, either siRNA-mediated downregulation or INH6’s chemical inhibition of Nek2 in MDA-MB-231 and Hs578t cells showed important EMT changes and decreased invasion and migration. We also showed that Slug and Zeb1 are involved in Nek2 mediated EMT, invasion, and migration. Besides its role in CA/CIN, Nek2 contributes to breast cancer progression through a novel EMT mediated mechanism.Yainyrette Rivera-RiveraMihaela MarinaShirley JusinoMiyoung LeeJaleisha Vélez VelázquezCamille Chardón-ColónGeraldine VargasJaya PadmanabhanSrikumar P. ChellappanHarold I. SaavedraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yainyrette Rivera-Rivera Mihaela Marina Shirley Jusino Miyoung Lee Jaleisha Vélez Velázquez Camille Chardón-Colón Geraldine Vargas Jaya Padmanabhan Srikumar P. Chellappan Harold I. Saavedra The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
description	Abstract Nek2 (NIMA‐related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dysfunction, and chromosome instability (CIN). Our group and others have suggested that Nek2 maintains high levels of CA/CIN, tumor growth, and drug resistance. We identified that Nek2 overexpression correlates with poor survival of breast cancer. However, the mechanisms driving these phenotypes are unknown. We now report that overexpression of Nek2 in MCF10A cells drives CA/CIN and aneuploidy. Besides, enhanced levels of Nek2 results in larger 3D acinar structures, but could not initiate tumors in a p53+/+ or a p53−/− xenograft model. Nek2 overexpression induced the epithelial-to-mesenchymal transition (EMT) while its downregulation reduced the expression of the mesenchymal marker vimentin. Furthermore, either siRNA-mediated downregulation or INH6’s chemical inhibition of Nek2 in MDA-MB-231 and Hs578t cells showed important EMT changes and decreased invasion and migration. We also showed that Slug and Zeb1 are involved in Nek2 mediated EMT, invasion, and migration. Besides its role in CA/CIN, Nek2 contributes to breast cancer progression through a novel EMT mediated mechanism.
format	article
author	Yainyrette Rivera-Rivera Mihaela Marina Shirley Jusino Miyoung Lee Jaleisha Vélez Velázquez Camille Chardón-Colón Geraldine Vargas Jaya Padmanabhan Srikumar P. Chellappan Harold I. Saavedra
author_facet	Yainyrette Rivera-Rivera Mihaela Marina Shirley Jusino Miyoung Lee Jaleisha Vélez Velázquez Camille Chardón-Colón Geraldine Vargas Jaya Padmanabhan Srikumar P. Chellappan Harold I. Saavedra
author_sort	Yainyrette Rivera-Rivera
title	The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
title_short	The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
title_full	The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
title_fullStr	The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
title_full_unstemmed	The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
title_sort	nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/349186be6236452795f3845aa7cf9050
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The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells

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