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CDK8 es un oncogén del cáncer colorrectal que regula la actividad de la beta-catenina
Ron Firestein1, Adam J Bass, So Young Kim
1Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature
|September 17, 2008
Resumen
Dirigirse a CDK8, un gen sobreexpresado en el cáncer de colon, inhibe la proliferación de las células cancerosas. Este hallazgo sugiere CDK8 como un objetivo terapéutico potencial para las neoplasias colorrectales WNT/beta-catenin-driven.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Genética del cáncer Genética del cáncer.
Sus antecedentes:
- La activación aberrante de la vía WNT / beta-catenina es un sello distintivo de casi todos los cánceres colorrectales.
- Mientras que la beta-catenina impulsa la tumorigénesis del colon, se necesitan cambios genéticos adicionales para la transformación maligna completa.
Objetivo del estudio:
- Identificar genes que modulan la actividad de la beta-catenina y que son esenciales para la proliferación de las células del cáncer de colon.
- Para investigar el papel de CDK8 en la progresión del cáncer colorrectal.
Principales métodos:
- Se realizaron dos pruebas de pérdida de función en células humanas de cáncer de colon.
- Comparó los genes identificados en pantalla con los datos de alteración del número de copias de muestras de cáncer de colon.
- Se evaluó el impacto de la supresión de CDK8 en la proliferación celular del cáncer de colon y los objetivos de beta-catenina.
Principales resultados:
- CDK8, que codifica un miembro del complejo mediador, se encuentra en 13q12.13, una región con ganancias recurrentes de número de copias en los cánceres de colon.
- La supresión de CDK8 inhibe la proliferación en las células de cáncer de colon con alta actividad de CDK8 y beta-catenina.
- La actividad de la kinasa CDK8 es crucial para la transformación impulsada por la beta-catenina y la expresión génica diana.
Conclusiones:
- CDK8 juega un papel importante en la proliferación de células de cáncer de colon y la transformación maligna.
- La orientación terapéutica de CDK8 puede ofrecer beneficios clínicos para los cánceres colorrectales con activación de la vía WNT/beta-catenina.
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