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Cyfip1 es un supresor de invasión putativo en cánceres epiteliales
Jose M Silva1, Elena Ezhkova, Javier Silva
1Watson School Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cell
|June 16, 2009
Resumen
Cyfip1, un gen supresor de tumores, se elimina con frecuencia en los cánceres epiteliales. Su expresión reducida perjudica la adhesión celular y promueve la invasión del cáncer, lo que sugiere su papel en la supresión de la propagación del tumor.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La identificación de los supresores de tumores es difícil debido a las numerosas alteraciones genéticas en el cáncer.
- Las deleciones cromosómicas en el cáncer pueden albergar genes supresores de tumores críticos.
Objetivo del estudio:
- Identificar nuevos genes supresores de tumores dentro de regiones eliminadas en cánceres humanos.
- Investigar el papel de Cyfip1 (proteína de interacción FMRP citoplasmática 1) en la progresión del cáncer epitelial.
Principales métodos:
- Análisis genómico de alta resolución para identificar regiones eliminadas.
- Estudio genético en dos etapas que utiliza la interferencia de ARN (RNAi) para el silenciamiento de genes.
- Estudios in vitro sobre la morfogénesis epitelial y estudios in vivo con Ras. oncogénico.
Principales resultados:
- Cyfip1, una subunidad del complejo WAVE que regula el citoesqueleto, se elimina con frecuencia en los cánceres epiteliales.
- La expresión reducida de CYFIP1 se correlaciona con la invasión tumoral y un mal pronóstico.
- El silenciamiento de Cyfip1 interrumpe la morfogénesis epitelial, la adhesión celular y las interacciones de la matriz celular-extracelular.
- La pérdida de Cyfip1 coopera con Ras oncogénico para impulsar la formación de carcinoma invasivo.
Conclusiones:
- Cyfip1 funciona como un supresor de tumores, específicamente un gen supresor de invasión.
- Las alteraciones en la dinámica de actina regulada por WAVE contribuyen a la invasión del cáncer a través de la adherencia celular deteriorada y las interacciones de la matriz.
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