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Rho GTPases in human carcinogenesis: a tale of excess

GTPasas Rho en carcinogénesis humana: una cuestión de exceso

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Abstract

Rho GTPases are proteins that in response to diverse stimuli control key signaling and structural aspects of the cell. Although early studies had proposed a role for Rho GTPases in cellular transformation, this effect was underestimated by the fact that no genetic mutations affecting Rho-encoding genes was found in human tumors. However, in recent years a high incidence of overexpression of different members of the family of Rho GTPases in human tumors has been detected which is leading to a great interest in the cellular effects elicited by these oncoproteins. As well, the characterization of downstream effectors and upstream regulators of Rho GTPases provides crucial clues on the specific cellular effects that permit aberrant cellular growth and tumorigenesis. A direct link between the functions of some of these signaling elements and regulation of the cell cycle, cytoskeletal rearrangements and cell adhesion has been observed in distinct types of human tumors. Provided this information, a number of drugs that affect Rho signaling at different levels have been described with promisingin vivo antitumoral activity. In this review, the current evidence of dysregulation of Rho signaling in human tumors is assembled.

Resumen

Las GTPasas Rho regulan un alto número de procesos de señalización y estructurales de la célula en respuesta a diversos estímulos. El hecho de que no se haya detectado mutación alguna en la secuencia primaria de ningún miembro de la familia de GT-Pasas Rho ha conllevado a que se subestimase su posible papel en la biología de diversos tumores humanos. Sin embargo, el creciente número de trabajos recientes que describen una elevada incidencia muy alta de sobreexpresión de las proteínas Rho en un alto número de tumores ha suscitado mucho interés en la comunidad científica. La caracterización de proteínas efectoras y de la señalización dependiente de Rho ha permitido identificar los mecanismos a través de los cuales esta familia de proteínas inducen una proliferación aberrante y, en última instancia, el desarrollo y progresión del tumor. La relación entre la actividad de alguna de las proteínas efectoras de Rho con el ciclo celular, reorganización del citoesqueleto y la adhesión celular ha sido observada en diversos tipos de tumores humanos. Además se ha sintetizado una serie de compuestos que afectan las rutas de señalización dependientes de Rho a varios niveles y que muestran una actividad antitumoralin vivo prometedora. En esta revisión realizamos un detallado resumen del conocimiento actual acerca de la desregulación de las proteínas Rho en tumores humanos.

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  1. Instituto de Investigaciones Biomédicas, CSIC, Madrid

    Salvador Aznar Benitah, Carolina Espina, Pilar F. Valerón & Juan Carlos Lacal

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  1. Salvador Aznar Benitah
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Correspondence to Juan Carlos Lacal.

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Benitah, S.A., Espina, C., Valerón, P.F. et al. Rho GTPases in human carcinogenesis: a tale of excess. Rev Oncol 5, 70–78 (2003). https://doi.org/10.1007/BF02728199

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