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Activation of KRAS promotes the mesenchymal features of basal-type breast cancer

Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscur...

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Autores principales: Kim, Rae-Kwon, Suh, Yongjoon, Yoo, Ki-Chun, Cui, Yan-Hong, Kim, Hyeonmi, Kim, Min-Jung, Gyu Kim, In, Lee, Su-Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314588/
https://www.ncbi.nlm.nih.gov/pubmed/25633745
http://dx.doi.org/10.1038/emm.2014.99
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author Kim, Rae-Kwon
Suh, Yongjoon
Yoo, Ki-Chun
Cui, Yan-Hong
Kim, Hyeonmi
Kim, Min-Jung
Gyu Kim, In
Lee, Su-Jae
author_facet Kim, Rae-Kwon
Suh, Yongjoon
Yoo, Ki-Chun
Cui, Yan-Hong
Kim, Hyeonmi
Kim, Min-Jung
Gyu Kim, In
Lee, Su-Jae
author_sort Kim, Rae-Kwon
collection PubMed
description Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscure. Here, we report that KRAS is a critical regulator for the maintenance of mesenchymal features in basal-type breast cancer cells. KRAS is preferentially activated in basal-type breast cancer cells as compared with luminal type. By loss and gain of KRAS, we found that KRAS is necessary and sufficient for the maintenance of mesenchymal phenotypes and metastatic ability through SLUG expression. Taken together, this study demonstrates that KRAS is a critical regulator for the metastatic behavior associated with mesenchymal features of breast cancer cells, implicating a novel therapeutic target for basal-type breast cancer.
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spelling pubmed-43145882015-02-11 Activation of KRAS promotes the mesenchymal features of basal-type breast cancer Kim, Rae-Kwon Suh, Yongjoon Yoo, Ki-Chun Cui, Yan-Hong Kim, Hyeonmi Kim, Min-Jung Gyu Kim, In Lee, Su-Jae Exp Mol Med Original Article Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscure. Here, we report that KRAS is a critical regulator for the maintenance of mesenchymal features in basal-type breast cancer cells. KRAS is preferentially activated in basal-type breast cancer cells as compared with luminal type. By loss and gain of KRAS, we found that KRAS is necessary and sufficient for the maintenance of mesenchymal phenotypes and metastatic ability through SLUG expression. Taken together, this study demonstrates that KRAS is a critical regulator for the metastatic behavior associated with mesenchymal features of breast cancer cells, implicating a novel therapeutic target for basal-type breast cancer. Nature Publishing Group 2015-01 2015-01-30 /pmc/articles/PMC4314588/ /pubmed/25633745 http://dx.doi.org/10.1038/emm.2014.99 Text en Copyright © 2015 KSBMB. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Kim, Rae-Kwon
Suh, Yongjoon
Yoo, Ki-Chun
Cui, Yan-Hong
Kim, Hyeonmi
Kim, Min-Jung
Gyu Kim, In
Lee, Su-Jae
Activation of KRAS promotes the mesenchymal features of basal-type breast cancer
title Activation of KRAS promotes the mesenchymal features of basal-type breast cancer
title_full Activation of KRAS promotes the mesenchymal features of basal-type breast cancer
title_fullStr Activation of KRAS promotes the mesenchymal features of basal-type breast cancer
title_full_unstemmed Activation of KRAS promotes the mesenchymal features of basal-type breast cancer
title_short Activation of KRAS promotes the mesenchymal features of basal-type breast cancer
title_sort activation of kras promotes the mesenchymal features of basal-type breast cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314588/
https://www.ncbi.nlm.nih.gov/pubmed/25633745
http://dx.doi.org/10.1038/emm.2014.99
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