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El fracaso de la citocinesis desencadena la activación de la vía supresora de tumores del hipocampo
Neil J Ganem1, Hauke Cornils1, Shang-Yi Chiu1
1Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|August 16, 2014
Resumen
Las células tetraploides, comunes en los tumores, activan la vía de Hippo debido a la falla de la citocinesis y los centrosomas adicionales. Esta vía, que involucra a LATS2, estabiliza p53 e inhibe YAP / TAZ, actuando como un mecanismo supresor de tumores.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología del cáncer Biología del cáncer.
- Genética La genética.
Sus antecedentes:
- La tetraploidía, caracterizada por la duplicación del genoma, se observa en aproximadamente el 37% de los tumores humanos y puede promover la tumorigénesis.
- Una barrera dependiente de p53 normalmente suprime la proliferación en las células tetraploides, pero los defectos celulares subyacentes y las vías de señalización siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Para identificar los defectos celulares y las vías de señalización que desencadenan la supresión del crecimiento en las células tetraploides.
- Para aclarar el papel de la vía de Hippo en la supresión del crecimiento de las células tetraploides y la supresión de tumores.
Principales métodos:
- Se utilizó el cribado de interferencia de ARN (RNAi) para identificar genes involucrados en la supresión del crecimiento celular tetraploide.
- Se emplean enfoques de evolución in vitro para estudiar los mecanismos adaptativos en las células tetraploides.
- Investigó la activación de la vía de Hippo tanto en células tetraploides cultivadas como en células tetraploides de origen natural.
Principales resultados:
- Se demostró que la falla de la citocinesis en las células tetraploides activa la vía supresora del tumor de Hippo.
- Se demostró que los centrosomas adicionales contribuyen a la inducción de la vía de Hippo alterando la señalización de proteínas G pequeñas y activando la LATS2 quinasa.
- Se confirmó que LATS2 estabiliza p53 e inhibe los reguladores transcripcionales YAP y TAZ.
Conclusiones:
- La vía de Hippo actúa como un mecanismo supresor tumoral crítico activado por la falla de la citocinesis y los centrosomas adicionales en las células tetraploides.
- Los hallazgos revelan cómo se suprimen las células tetraploides y sugieren posibles mecanismos adaptativos para que las células tumorales evadan esta regulación.
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