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CD95 promueve el crecimiento tumoral
Lina Chen1, Sun-Mi Park, Alexei V Tumanov
1The Ben May Department for Cancer Research, The University of Chicago, 924 E 57th Street, Chicago, Illinois 60637, USA.
Nature
|May 28, 2010
Resumen
La señalización del receptor CD95 (Fas), a menudo relacionada con la muerte celular, promueve sorprendentemente el crecimiento tumoral. Inhibir CD95, no potenciarlo, puede ser una estrategia viable para el tratamiento del cáncer.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del cáncer Biología del cáncer.
- La señalización molecular.
Sus antecedentes:
- El receptor CD95 (Fas) es crucial para la homeostasis del sistema inmunológico a través de la apoptosis.
- Las células tumorales a menudo desregulan CD95 o resisten la apoptosis, lo que sugiere que la pérdida de CD95 ayuda a la evasión tumoral.
- Paradójicamente, muchos cánceres expresan CD95 y su ligando (CD95L), lo que insinúa funciones no apoptóticas.
Objetivo del estudio:
- Para investigar el papel de la señalización CD95 en el crecimiento tumoral.
- Para determinar si CD95 promueve la tumorigénesis a través de vías no apoptóticas.
- Evaluar el CD95 como un objetivo terapéutico en el cáncer.
Principales métodos:
- Análisis de la expresión de CD95 y la sensibilidad a la apoptosis en las células cancerosas.
- Investigando la señalización CD95 en modelos de ratón de cáncer de ovario y hígado.
- Elucidando la vía de señalización aguas abajo (JNK/Jun) involucrada en la tumorigénesis mediada por CD95.
Principales resultados:
- Las células cancerosas dependen de la actividad constitutiva de CD95, estimulada por CD95L producido por el cáncer, para el crecimiento.
- La pérdida de CD95 redujo significativamente la incidencia del cáncer y el tamaño del tumor en modelos de ratón.
- La promoción tumoral impulsada por CD95 involucra las vías de señalización JNK y Jun.
Conclusiones:
- CD95 juega un papel pro-tumorigénico en el desarrollo y la progresión del cáncer.
- Dirigirse a la actividad de CD95, en lugar de mejorarla, es una estrategia terapéutica prometedora.
- Comprender las funciones no apoptóticas de CD95 es fundamental para desarrollar tratamientos efectivos contra el cáncer.
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