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La histona desacetilasa SIRT6 es un supresor tumoral que controla el metabolismo del cáncer
Carlos Sebastián1, Bernadette M M Zwaans, Dafne M Silberman
1The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Cell
|December 11, 2012
Resumen
SIRT6 actúa como un supresor de tumores mediante la regulación del metabolismo de las células cancerosas. La pérdida de SIRT6 promueve el crecimiento tumoral y la agresividad, destacando su papel crítico en el desarrollo y la progresión del cáncer.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- El metabolismo del cáncer.
Sus antecedentes:
- La reprogramación del metabolismo celular es crucial para el desarrollo del tumor (efecto Warburg).
- Los mecanismos moleculares que controlan los cambios metabólicos en el cáncer siguen siendo en gran medida desconocidos.
- El papel de SIRT6 en el metabolismo del cáncer no se ha aclarado previamente.
Objetivo del estudio:
- Para identificar los reguladores moleculares del metabolismo de las células cancerosas.
- Para investigar la función de SIRT6 como supresor de tumores.
- Determinar el papel de SIRT6 en el establecimiento y mantenimiento del cáncer.
Principales métodos:
- Utilizó un alelo SIRT6 condicional para estudios in vivo.
- Se evaluó la formación tumoral, el crecimiento y la agresividad tras la deleción de SIRT6.
- Investigó la regulación de la glicolisis aeróbica por parte de SIRT6 y la actividad transcripcional de MYC.
- Se analizó la expresión de SIRT6 en cánceres humanos y se correlacionó con el pronóstico del paciente.
Principales resultados:
- La deleción de SIRT6 in vivo aumentó significativamente el número, el tamaño y la agresividad del tumor.
- Las células deficientes de SIRT6 exhibieron una mayor glucólisis y crecimiento tumoral.
- SIRT6 fue identificado como un represor de la actividad transcripcional de MYC, regulando el metabolismo de los ribosomas.
- La desregulación de la SIRT6 en los cánceres humanos se correlacionó con un mal pronóstico y una reducción de la supervivencia libre de tumores.
Conclusiones:
- SIRT6 es un supresor tumoral crítico que suprime el metabolismo del cáncer.
- La pérdida de SIRT6 promueve tanto el establecimiento como el mantenimiento del cáncer.
- Los niveles de expresión de SIRT6 sirven como un marcador de pronóstico para varios cánceres humanos.
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