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Gang Xiao¹, Lai N Chan¹, Lars Klemm¹

¹Department of Systems Biology, Beckman Research Institute, and City of Hope Comprehensive Cancer Center, Monrovia, CA 91016, USA.

|March 20, 2018

Resumen

La serina/treonina-proteína fosfatasa 2A (PP2A) es crucial en los tumores de células B, redirigiendo la glucosa a la vía de la pentosa fosfato (PPP) para la homeostasis redox. La inhibición de PP2A y G6PD ofrece una estrategia terapéutica para las neoplasias de células B.

Área de la Ciencia:

En el campo de la oncología
Inmunología
Las vías metabólicas

Sus antecedentes:

La activación de las células B y el cáncer aumentan las demandas metabólicas y el estrés oxidativo.
La serina/treonina-proteína fosfatasa 2A (PP2A) es un supresor tumoral conocido, pero su papel en los tumores de células B es esencial.
Las células B tienen una actividad constitutivamente baja de la vía pentosa fosfato (PPP) debido a la represión transcripcional por PAX5 e IKZF1.

Objetivo del estudio:

Investigar el papel de PP2A en el metabolismo de las células B y la homeostasis redox.
Identificar las vulnerabilidades en las neoplasias de células B que pueden ser tratadas terapéuticamente.

Principales métodos:

Estudios genéticos en tumores de células B.
Análisis de las vías de utilización del carbono de la glucosa (glucólisis y PPP).
Evaluación del estrés oxidativo y de los mecanismos de protección antioxidante.

Principales resultados:

PP2A es esencial en los tumores de células B, redirigiendo el metabolismo de la glucosa de la glucólisis a la PPP.
Esta redirección ayuda a las células B a manejar el estrés oxidativo.
La represión transcripcional específica de las enzimas PPP en las células B crea una vulnerabilidad que puede ser explotada en tumores malignos de células B.
La inhibición de PP2A y G6PD muestra potencial terapéutico.

Conclusiones:

La vía de la pentosa fosfato (PPP) actúa como un guardián en las neoplasias de células B.
Dirigirse a PP2A y G6PD con moléculas pequeñas es una estrategia terapéutica prometedora para los cánceres de células B.

Palabras clave:

Tumores malignos de las células B G6PD (en inglés)El PP2A metabolismo de la glucosa Vulnerabilidad específica del linaje La homeostasis redox Represión de la transcripción

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