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FMN2 produce actina perinuclear para proteger los núcleos durante la migración confinada y promover la metástasis
Colleen T Skau1, Robert S Fischer1, Pinar Gurel1
1Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|November 15, 2016
Resumen
Un sistema de actina perinuclear recientemente descubierto, impulsado por FMN2, protege los núcleos celulares durante la migración en espacios confinados. Este mecanismo es crucial para la supervivencia y la metástasis de las células cancerosas.
Área de la Ciencia:
- Biología celular
- La biofísica
- Investigación del cáncer
Sus antecedentes:
- La migración celular en entornos 3D confinados es vital para los procesos fisiológicos y la propagación del tumor.
- La integridad nuclear se desafía durante la migración, lo que puede conducir a daños en el ADN.
- La dinámica del citoesqueleto actino juega un papel clave en la mecánica celular y la migración.
Objetivo del estudio:
- Identificar los mecanismos citoesqueléticos que protegen el núcleo durante la migración en microambientes 3D confinados.
- Investigar el papel de la proteína de la familia de las forminas FMN2 en la protección nuclear y la supervivencia celular.
- Para determinar la participación de FMN2 en la metástasis de las células del melanoma.
Principales métodos:
- Utilizó imágenes de células vivas y microscopía para observar las estructuras citoesqueléticas y la dinámica nuclear.
- Investigó la función de FMN2 utilizando manipulación genética (disrupción) en modelos celulares y animales.
- Niveles de expresión de FMN2 analizados en muestras de melanoma humano.
Principales resultados:
- Descubrió un nuevo sistema de actina perinuclear / adhesión focal (FA) regulado por FMN2.
- Este sistema dependiente de FMN2 controla la forma y el posicionamiento del núcleo.
- FMN2 protege el núcleo del daño y las rupturas de doble cadena de ADN en la migración 3D confinada.
- La FMN2 está regulada al alza en los melanomas humanos; su alteración inhibe la extravasación celular del melanoma y la metástasis pulmonar en ratones.
Conclusiones:
- FMN2 es esencial para la generación de un sistema protector de actina perinuclear/FA durante la migración celular confinada.
- Este sistema salvaguarda la integridad del núcleo y el ADN, promoviendo la supervivencia celular.
- FMN2 juega un papel importante en la promoción de la metástasis de las células cancerosas, destacando su potencial como objetivo terapéutico.
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