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La activación e inactivación de Rac controla la plasticidad del movimiento de las células tumorales
Victoria Sanz-Moreno1, Gilles Gadea, Jessica Ahn
1Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK.
Cell
|November 6, 2008
Resumen
Las células tumorales cambian entre el movimiento mesenquimal y el movimiento ameboide mediante la regulación de las vías de señalización Rho y Rac. Este estudio identifica a los actores moleculares clave que controlan estos modos críticos de migración celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Investigación del cáncer Investigación del cáncer.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las células tumorales exhiben modos distintos de migración: mesenquimales y ameboides.
- El movimiento mesenquimal involucra células alargadas, proteólisis y señalización Rac.
- El movimiento del amoeboide se caracteriza por células redondeadas, señalización de Rho-cinasa y alta contractilidad de la actomyosina.
Objetivo del estudio:
- Aclarar los mecanismos moleculares que rigen la interconversión entre el movimiento de células tumorales mesenquimales y ameboides.
- Identificar las vías de señalización clave y las proteínas que regulan estos distintos modos de migración celular.
Principales métodos:
- Investigó los roles de las GTPasas Rac y la señalización de Rho-cinasa en la regulación de la morfología y el movimiento celular.
- Utilizamos complejos moleculares que involucran NEDD9, DOCK3, WAVE2 y ARHGAP22 para estudiar la actividad de Rac y Rho.
- Analizó la interacción entre las vías de señalización Rho y Rac en el control de la migración de las células tumorales.
Principales resultados:
- El movimiento mesenquimal es impulsado por la activación de Rac a través del complejo NEDD9-DOCK3, que envía señales a través de WAVE2.2.
- La activación de Rac suprime la contractilidad de la actomyosina, inhibiendo el movimiento ameboide.
- La señalización de la ro-cinasa activa ARHGAP22, un Rac GAP, que suprime el movimiento mesenquimal inactivando Rac.
Conclusiones:
- Los modos de migración de las células tumorales están determinados por una interacción dinámica entre la señalización Rho y Rac.
- Comprender estos mecanismos de conmutación proporciona información sobre la metástasis del melanoma y las posibles dianas terapéuticas.
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