The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function

It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which t...

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Detalles Bibliográficos
Autores: Lorenzo-Martín, L. Francisco, Menacho-Márquez, Mauricio, Fernández-Parejo, Natalia, Rodríguez-Fdez, Sonia, Pascual, Gloria, Abad, Antonio, Crespo, Piero, Dosil, Mercedes, Benitah, Salvador A., Bustelo, Xosé R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::50e977f8d65e4f41696c9d6c7a110323
Acceso en línea:http://hdl.handle.net/10261/283396
Access Level:acceso abierto
Palabra clave:Cancer stem cells
Experimental organisms
RHO signalling
Squamous cell carcinoma
Descripción
Sumario:It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which the activity of guanosine nucleotide exchange factors of the Vav subfamily has been manipulated using both gain- and loss-of-function strategies. These experiments indicate that Vav2 and Vav3 regulate the number, functional status, and responsiveness of hair follicle bulge stem cells. This is linked to gene expression programs related to the reinforcement of the identity and the quiescent state of normal SSCs. By contrast, in the case of cancer stem cells, they promote transcriptomal programs associated with the identity, activation state, and cytoskeletal remodeling. These results underscore the role of these Rho exchange factors in the regulation of normal and tumor epidermal stem cells.