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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
El IKKalpha activado por citoquinas nucleares controla la metástasis del cáncer de próstata al reprimir la actividad
Jun-Li Luo1, Wei Tan, Jill M Ricono
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA.
Nature
|March 23, 2007
Resumen
La inflamación promueve la metástasis del cáncer de próstata mediante la activación de la kinasa alfa IkappaB (IKKalpha), que suprime el supresor de la metástasis de Maspin. Esta vía enlaza las células inflamatorias con la progresión y la metástasis del cáncer de próstata.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- Se sabe que la inflamación promueve el crecimiento tumoral a través de las vías NF-kappaB.
- La señalización de NF-kappaB está implicada en la transición epitelial-mesenquimal y la metástasis.
- Un vínculo mecánico directo entre la inflamación y la metástasis del cáncer sigue siendo elusivo.
Objetivo del estudio:
- Para investigar el papel de la kinasa alfa IkappaB (IKKalpha) en la progresión y metástasis del cáncer de próstata.
- Aclarar los mecanismos moleculares por los cuales la inflamación influye en la metástasis del cáncer de próstata.
Principales métodos:
- Utilizó modelos de ratón TRAMP de cáncer de próstata.
- Investigó el papel de la activación de IKKalpha y sus efectos posteriores en la expresión de Maspin.
- Niveles de IKKalpha nucleares correlacionados con progresión metastásica en muestras de cáncer de próstata en ratones y humanos.
Principales resultados:
- La inhibición de la activación de IKKalpha redujo significativamente el crecimiento y la metástasis del cáncer de próstata en ratones TRAMP.
- La disminución de la metástasis se correlacionó con el aumento de la expresión de Maspin; la ablación de Maspin restauró el potencial metastásico.
- El IKKalpha activado por RANKL inhibe la expresión de Maspin, lo que requiere la translocación nuclear del IKKalpha activo.
Conclusiones:
- La activación nuclear de IKKalpha, impulsada por células inflamatorias que se infiltran en el tumor y expresan RANKL, inhibe la transcripción de Maspin.
- Esta vía promueve la metástasis del cáncer de próstata mediante la supresión de Maspin.
- Dirigirse al eje RANKL-IKKalpha-Maspin puede ofrecer estrategias terapéuticas para la metástasis del cáncer de próstata.
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