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El colapso catastrófico de la envoltura nuclear en los micronúcleos de las células cancerosas
Emily M Hatch1, Andrew H Fischer, Thomas J Deerinck
1Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|July 6, 2013
Resumen
Los micronúcleos (MN) pueden colapsar irreversiblemente durante la interfase debido a defectos de la envoltura nuclear (NE), lo que perjudica la función nuclear y causa daño al ADN. Este colapso NE está vinculado a la inestabilidad genómica y puede servir como un biomarcador en el cáncer.
Área de la Ciencia:
- Biología celular Biología celular.
- Investigación de Investigación del Cáncer.
- La genómica es la genómica.
Sus antecedentes:
- Los cromosomas mal segregados forman micronúcleos (MN) durante la salida mitótica.
- Los micronúcleos (MN) exhiben una función reducida a pesar de la similitud estructural con los núcleos primarios.
Objetivo del estudio:
- Investigar la integridad estructural y funcional de MN durante la interfase.
- Para identificar los mecanismos subyacentes a la disfunción MN y su papel potencial en el cáncer.
Principales métodos:
- Imágenes de células vivas para observar la dinámica del MN.
- Inmunofluorescencia para evaluar la envoltura nuclear y el montaje de la lámina.
- Los ensayos de daño al ADN cuantifican la inestabilidad genómica.
Principales resultados:
- Más del 60% de las MN sufren un colapso irreversible de NE durante la interfase.
- Los defectos en el ensamblaje de la lámina nuclear desencadenan la interrupción de MN.
- La interrupción de la MN conduce a la compactación de la cromatina, la invasión de los túbulos ER, la reducción de la función nuclear y el daño masivo del ADN.
- La MN interrumpida se encuentra en el cáncer de pulmón de células no pequeñas, en correlación con la inestabilidad genómica.
Conclusiones:
- El colapso del NE es un evento crítico que causa disfunción del MN.
- La organización anormal de NE en MN está relacionada con la aneuploidía y la inestabilidad genómica.
- La MN interrumpida representa un biomarcador potencial para la inestabilidad genómica en tumores sólidos.
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