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Un punto de control mecánico controla el crecimiento multicelular a través de la regulación YAP / TAZ por factores de
Mariaceleste Aragona1, Tito Panciera1, Andrea Manfrin1
1Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy.
Cell
|August 20, 2013
Resumen
La arquitectura de los tejidos y las fuerzas mecánicas regulan la proliferación celular a través de la señalización YAP / TAZ. Las señales físicas como el estiramiento y la rigidez controlan el crecimiento celular, previniendo enfermedades como el cáncer al mantener el control espacial.
Área de la Ciencia:
- Biología celular Biología celular.
- La biofísica es la biofísica.
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- Las decisiones celulares sobre la proliferación o la detención del crecimiento están reguladas espacialmente dentro de los tejidos.
- La interrupción de este control espacial es una característica clave de las enfermedades, especialmente el cáncer.
- Los mecanismos que establecen estos patrones espaciales siguen siendo incompletamente entendidos.
Objetivo del estudio:
- Investigar cómo las características físicas y arquitectónicas de las láminas multicelulares influyen en la capacidad de proliferación celular.
- Aclarar el papel de la regulación mecánica de YAP/TAZ (proteína asociada a sí/T-y-zendrina) en el control de los patrones de crecimiento celular.
Principales métodos:
- Investigó la regulación mecánica de la actividad YAP / TAZ en respuesta a señales físicas en hojas multicelulares.
- Se identificaron proteínas clave de unión a la F-actina (Cofilin, CapZ, Gelsolin) involucradas en la modulación de la actividad de YAP/TAZ.
- Examinó la influencia de las tensiones mecánicas como el estiramiento, la curvatura y la rigidez de la matriz extracelular.
Principales resultados:
- La actividad YAP/TAZ está restringida a las células que experimentan tensiones mecánicas, como el estiramiento o la residencia en los bordes/curvaturas de las láminas epiteliales.
- La rigidez de la matriz extracelular tiene un impacto significativo en la localización y actividad de YAP/TAZ.
- Cofilin, CapZ y Gelsolin actúan como reguladores críticos, limitando la actividad de YAP / TAZ en condiciones de bajo estrés mecánico, incluida la inhibición de la proliferación por contacto.
Conclusiones:
- Las características físicas y arquitectónicas de los tejidos regulan mecánicamente YAP/TAZ, controlando así la proliferación celular.
- Las fuerzas mecánicas se identifican como reguladores generales de YAP / TAZ en contextos multicelulares.
- Esta regulación mecánica influye en la capacidad de respuesta celular a las vías de señalización Hippo, WNT y GPCR.
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