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El mutante p53 impulsa la invasión promoviendo el reciclaje de integrina
Patricia A J Muller1, Patrick T Caswell, Brendan Doyle
1The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Cell
|January 13, 2010
Resumen
Las proteínas p53 mutantes impulsan la invasión y la metástasis del cáncer al mejorar las vías de señalización celular. Dirigirse a la integrina y a los receptores del FEAG puede ofrecer nuevas terapias contra el cáncer.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- p53 es una proteína supresora de tumores crucial que con frecuencia se inactiva en los cánceres por mutaciones de mal sentido en el gen TP53.
- Las proteínas p53 mutantes no solo pierden funciones supresoras de tumores, sino que también ganan actividades pro-metastásicas, contribuyendo a la progresión del cáncer.
Objetivo del estudio:
- Investigar los mecanismos por los cuales la p53 mutante promueve la invasión y la metástasis de las células cancerosas.
- Identificar las vías de señalización clave y los actores moleculares involucrados en la oncogénesis impulsada por mutantes p53.
Principales métodos:
- Análisis de la invasión celular, la migración y el comportamiento metastásico en presencia del mutante p53.3.
- Investigación de las vías de tráfico y señalización de la integrina y del receptor del factor de crecimiento epidérmico (EGFR).
- Evaluación del papel de la proteína de acoplamiento Rab (RCP) y TAp63 en las funciones mutantes de p53.
Principales resultados:
- La expresión mutante de p53 mejora la invasión celular, interrumpe la direccionalidad de la migración y promueve el comportamiento metastásico.
- Estos efectos están mediados por un aumento de la integrina y el tráfico de EGFR, dependiente de la RCP, que conduce a la señalización constitutiva de EGFR / integrina.
- La p53 mutante promueve la invasión a través de la inhibición de TAp63; la pérdida simultánea de p53 y TAp63 imita los fenotipos de la p53 mutante.
Conclusiones:
- El mutante p53 impulsa activamente la progresión del cáncer mediante la reprogramación de la señalización celular y las vías de tráfico.
- La orientación a la alfa5/beta1-integrina y/o al EGFR representa una estrategia terapéutica potencial para los cánceres que expresan el mutante p53.
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