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La función metabólica de la ciclina D3-CDK6 en la supervivencia de las células cancerosas
Haizhen Wang1,2, Brandon N Nicolay3, Joel M Chick4
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Nature
|June 14, 2017
Resumen
La ciclina D3-CDK6 quinasa regula el metabolismo de las células cancerosas mediante la reorientación de la glucólisis. La inhibición de este complejo agota los antioxidantes, aumenta las especies reactivas de oxígeno y causa la muerte de las células cancerosas.
Área de la Ciencia:
- En el campo de la oncología
- Biología molecular
- Metabolismo del cáncer
Sus antecedentes:
- Las ciclinas de tipo D y las cinasas dependientes de la ciclina (CDK) 4/6 son cruciales para la proliferación celular.
- Los inhibidores de la CDK4/ 6 son prometedores en los ensayos clínicos de cáncer.
Objetivo del estudio:
- Investigar el papel de la ciclina D3-CDK6 en el metabolismo de las células cancerosas y sus implicaciones terapéuticas.
Principales métodos:
- Se utilizaron células cancerosas humanas y xenografts derivados de pacientes en ratones.
- Se analizó el efecto de la ciclina D3-CDK6 en las enzimas glicolíticas y las vías metabólicas.
Principales resultados:
- La ciclina D3-CDK6 fosforila y inhibe la 6-fosfructokinasa y la piruvato quinasa M2.
- Esto redirige los intermedios a las vías de la pentosa fosfato (PPP) y la serina.
- La inhibición de la ciclina D3-CDK6 agota el NADPH y el glutatión, aumentando las especies reactivas de oxígeno e induciendo la apoptosis.
Conclusiones:
- La ciclina D3-CDK6 vincula el ciclo celular y el metabolismo, actuando como una oncoproteína.
- La medición de los niveles de ciclina D3-CDK6 puede identificar tumores que responden a la terapia de inhibición de CDK4/6.
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