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La activación independiente de almacenamiento de Orai1 por SPCA2 en los tumores mamarios
Mingye Feng1, Desma M Grice, Helen M Faddy
1Department of Physiology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA.
Cell
|October 5, 2010
Resumen
La regulación ascendente de la vía secretora Ca2+-ATPasa 2 (SPCA2) promueve el cáncer de mama al aumentar la afluencia de calcio a través de Orai1. La supresión de SPCA2 reduce los niveles de calcio y el crecimiento tumoral, revelando una nueva vía de tumorigénesis.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología celular Biología celular.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- Los iones de calcio (Ca2+) son mensajeros secundarios vitales que regulan los procesos celulares.
- Las dinámicas citosólicas alteradas de Ca2+ están implicadas en la tumorigénesis, afectando la motilidad, la proliferación y la apoptosis.
Objetivo del estudio:
- Para investigar el papel de la vía secretora Ca2+-ATPasa 2 (SPCA2) en el cáncer de mama.
- Para aclarar el mecanismo por el cual SPCA2 influye en la señalización del calcio y la tumorigenicidad.
Principales métodos:
- Análisis de la expresión de SPCA2 en células de cáncer de mama y tumores.
- Ensayos funcionales para evaluar el impacto de la supresión de SPCA2 en los niveles de Ca2+ y la tumorigenicidad.
- Investigación de la interacción entre SPCA2 y el canal Ca2+ operado en el almacén Orai1.1.
Principales resultados:
- SPCA2 es regulado al alza en las células de cáncer de mama y tumores.
- La supresión de SPCA2 disminuye los niveles basales de Ca2+ y atenúa la tumorigenicidad.
- SPCA2 mejora la afluencia de Ca2+ a través de Orai1, independientemente de las reservas de ER Ca2+ y las proteínas STIM.
- La unión del extremo N de SPCA2 a Orai1 activa el influjo de Ca2+.
Conclusiones:
- El complejo SPCA2-Orai1 forma una nueva vía de señalización que promueve la tumorigénesis.
- Esta vía involucra la señalización constitutiva de Ca2+ independiente de la tienda.
- Dirigirse a la interacción SPCA2-Orai1 puede ofrecer una estrategia terapéutica para el cáncer de mama.
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