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NLRC3 es un sensor inhibidor de las vías PI3K-mTOR en el cáncer
Rajendra Karki1, Si Ming Man1, R K Subbarao Malireddi1
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nature
|December 13, 2016
Resumen
El dominio de unión de nucleótidos y las proteínas de repetición ricas en leucina (NLR) regulan la inmunidad y la inflamación. La pérdida de NLRC3 aumenta la susceptibilidad a la colitis y al cáncer colorrectal al promover la activación de la vía mTOR.
Área de la Ciencia:
- Inmunología
- Biología molecular
- Gastroenterología
Sus antecedentes:
- El dominio de unión de nucleótidos y las repeticiones ricas en leucina (NLR) son sensores citoplasmáticos cruciales para la inmunidad y la homeostasis.
- La desregulación de los NLR contribuye a las enfermedades inflamatorias, autoinmunes y cancerosas.
- NLRC3, un NLR mal caracterizado, está regulado a la baja en los tejidos de cáncer colorrectal.
Objetivo del estudio:
- Investigar el papel de NLRC3 en la homeostasis intestinal y el desarrollo del cáncer colorrectal.
- Para aclarar los mecanismos moleculares por los cuales NLRC3 regula las vías celulares.
- Determinar el potencial terapéutico del NLRC3 en la prevención del cáncer.
Principales métodos:
- Se han generado y analizado ratones con deficiencia de NLRC3.
- Evaluación de la susceptibilidad a la colitis y a la tumorigénesis colorrectal.
- Se investigó la interacción de NLRC3 con las vías de señalización PI3K/AKT/mTOR en los enterocitos.
Principales resultados:
- Los ratones con deficiencia de NLRC3 presentan una mayor susceptibilidad a la colitis y al cáncer colorrectal.
- NLRC3 funciona principalmente en los enterocitos para suprimir la señalización mTOR, la proliferación celular y la formación de organoides.
- NLRC3 se asocia con PI3Ks, inhibiendo la activación de AKT aguas abajo del factor de crecimiento y la señalización del receptor Toll-like 4.
Conclusiones:
- NLRC3 actúa como un inhibidor crítico de la vía PI3K/AKT/mTOR en el epitelio intestinal.
- NLRC3 juega un papel protector contra la colitis y el desarrollo del cáncer colorrectal.
- Dirigirse a NLRC3 puede ofrecer una nueva estrategia para la prevención y el tratamiento del cáncer colorrectal.
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