The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b

Abstract Metastasis is the main cause of death in cancer patients, including breast cancer (BC). Despite recent progress in understanding the biological and molecular determinants of BC metastasis, effective therapeutic treatments are yet to be developed. Among the multitude of molecular mechanisms...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Khalid Sossey-Alaoui, Elzbieta Pluskota, Dorota Szpak, William P. Schiemann, Edward F. Plow
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9e7d9b1f90f44759827faaae4b78ccd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d9e7d9b1f90f44759827faaae4b78ccd
record_format	dspace
spelling	oai:doaj.org-article:d9e7d9b1f90f44759827faaae4b78ccd2021-12-02T11:41:14ZThe Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b10.1038/s41598-018-25373-02045-2322https://doaj.org/article/d9e7d9b1f90f44759827faaae4b78ccd2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25373-0https://doaj.org/toc/2045-2322Abstract Metastasis is the main cause of death in cancer patients, including breast cancer (BC). Despite recent progress in understanding the biological and molecular determinants of BC metastasis, effective therapeutic treatments are yet to be developed. Among the multitude of molecular mechanisms that regulate cancer metastasis, the epithelial-to-mesenchymal transition (EMT) program plays a key role in the activation of the biological steps leading to the metastatic phenotype. Kindlin-2 has been associated with the pathogenesis of several types of cancers, including BC. The role of Kindlin-2 in the regulation of BC metastasis, and to a lesser extent in EMT is not well understood. In this study, we show that Kindlin-2 is closely associated with the development of the metastatic phenotype in BC. We report that knockout of Kindlin-2 in either human or mouse BC cells, significantly inhibits metastasis in both human and mouse models of BC metastasis. We also report that the Kindlin-2-mediated inhibition of metastasis is the result of inhibition of expression of key molecular markers of the EMT program. Mechanistically, we show that miR-200b, a master regulator of EMT, directly targets and inhibits the expression of Kindlin-2, leading to the subsequent inhibition of EMT and metastasis. Together, our data support the targeting of Kindlin-2 as a therapeutic strategy against BC metastasis.Khalid Sossey-AlaouiElzbieta PluskotaDorota SzpakWilliam P. SchiemannEdward F. PlowNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Khalid Sossey-Alaoui Elzbieta Pluskota Dorota Szpak William P. Schiemann Edward F. Plow The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
description	Abstract Metastasis is the main cause of death in cancer patients, including breast cancer (BC). Despite recent progress in understanding the biological and molecular determinants of BC metastasis, effective therapeutic treatments are yet to be developed. Among the multitude of molecular mechanisms that regulate cancer metastasis, the epithelial-to-mesenchymal transition (EMT) program plays a key role in the activation of the biological steps leading to the metastatic phenotype. Kindlin-2 has been associated with the pathogenesis of several types of cancers, including BC. The role of Kindlin-2 in the regulation of BC metastasis, and to a lesser extent in EMT is not well understood. In this study, we show that Kindlin-2 is closely associated with the development of the metastatic phenotype in BC. We report that knockout of Kindlin-2 in either human or mouse BC cells, significantly inhibits metastasis in both human and mouse models of BC metastasis. We also report that the Kindlin-2-mediated inhibition of metastasis is the result of inhibition of expression of key molecular markers of the EMT program. Mechanistically, we show that miR-200b, a master regulator of EMT, directly targets and inhibits the expression of Kindlin-2, leading to the subsequent inhibition of EMT and metastasis. Together, our data support the targeting of Kindlin-2 as a therapeutic strategy against BC metastasis.
format	article
author	Khalid Sossey-Alaoui Elzbieta Pluskota Dorota Szpak William P. Schiemann Edward F. Plow
author_facet	Khalid Sossey-Alaoui Elzbieta Pluskota Dorota Szpak William P. Schiemann Edward F. Plow
author_sort	Khalid Sossey-Alaoui
title	The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
title_short	The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
title_full	The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
title_fullStr	The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
title_full_unstemmed	The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
title_sort	kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through mir-200b
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d9e7d9b1f90f44759827faaae4b78ccd
work_keys_str_mv	AT khalidsosseyalaoui thekindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT elzbietapluskota thekindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT dorotaszpak thekindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT williampschiemann thekindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT edwardfplow thekindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT khalidsosseyalaoui kindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT elzbietapluskota kindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT dorotaszpak kindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT williampschiemann kindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b AT edwardfplow kindlin2regulationofepithelialtomesenchymaltransitioninbreastcancermetastasisismediatedthroughmir200b
_version_	1718395430525468672

The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b

Ejemplares similares