The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.

The catalytic activity of GDP/GTP exchange factors (GEFs) is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we h...

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Autores principales:	Mauricio Menacho-Márquez, Ramón García-Escudero, Virginia Ojeda, Antonio Abad, Pilar Delgado, Clotilde Costa, Sergio Ruiz, Balbino Alarcón, Jesús M Paramio, Xosé R Bustelo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e74b0d4836c441568451f8d3957139dd
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spelling	oai:doaj.org-article:e74b0d4836c441568451f8d3957139dd2021-11-18T05:37:55ZThe Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.1544-91731545-788510.1371/journal.pbio.1001615https://doaj.org/article/e74b0d4836c441568451f8d3957139dd2013-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935450/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The catalytic activity of GDP/GTP exchange factors (GEFs) is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily exert such specific roles in skin cancer. Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors. Transcriptomal profiling and signaling experiments indicate such function is linked to the engagement of, and subsequent participation in, keratinocyte-based autocrine/paracrine programs that promote epidermal proliferation and recruitment of pro-inflammatory cells. This is a pathology-restricted mechanism because the loss of Vav proteins does not cause alterations in epidermal homeostasis. These results reveal a previously unknown Rho GEF-dependent pro-tumorigenic mechanism that influences the biology of cancer cells and their microenvironment. They also suggest that anti-Vav therapies may be of potential interest in skin tumor prevention and/or treatment.Mauricio Menacho-MárquezRamón García-EscuderoVirginia OjedaAntonio AbadPilar DelgadoClotilde CostaSergio RuizBalbino AlarcónJesús M ParamioXosé R BusteloPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 7, p e1001615 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Mauricio Menacho-Márquez Ramón García-Escudero Virginia Ojeda Antonio Abad Pilar Delgado Clotilde Costa Sergio Ruiz Balbino Alarcón Jesús M Paramio Xosé R Bustelo The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
description	The catalytic activity of GDP/GTP exchange factors (GEFs) is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily exert such specific roles in skin cancer. Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors. Transcriptomal profiling and signaling experiments indicate such function is linked to the engagement of, and subsequent participation in, keratinocyte-based autocrine/paracrine programs that promote epidermal proliferation and recruitment of pro-inflammatory cells. This is a pathology-restricted mechanism because the loss of Vav proteins does not cause alterations in epidermal homeostasis. These results reveal a previously unknown Rho GEF-dependent pro-tumorigenic mechanism that influences the biology of cancer cells and their microenvironment. They also suggest that anti-Vav therapies may be of potential interest in skin tumor prevention and/or treatment.
format	article
author	Mauricio Menacho-Márquez Ramón García-Escudero Virginia Ojeda Antonio Abad Pilar Delgado Clotilde Costa Sergio Ruiz Balbino Alarcón Jesús M Paramio Xosé R Bustelo
author_facet	Mauricio Menacho-Márquez Ramón García-Escudero Virginia Ojeda Antonio Abad Pilar Delgado Clotilde Costa Sergio Ruiz Balbino Alarcón Jesús M Paramio Xosé R Bustelo
author_sort	Mauricio Menacho-Márquez
title	The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
title_short	The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
title_full	The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
title_fullStr	The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
title_full_unstemmed	The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
title_sort	rho exchange factors vav2 and vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e74b0d4836c441568451f8d3957139dd
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The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.

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