Una fosfatasa PTEN secretada que entra en las células para alterar la señalización y la supervivencia
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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Benjamin D Hopkins1, Barry Fine, Nicole Steinbach
1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.
Science (New York, N.Y.)
|June 8, 2013
Resumen
Los investigadores descubrieron PTEN-Long, una nueva variante del supresor de tumores PTEN. Esta variante puede entrar en las células e inhibir el crecimiento del cáncer, ofreciendo nuevas terapias potenciales contra el cáncer.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Oncología Oncología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El gen PTEN (homólogo de la fosfatasa y la tensina en el cromosoma diez) es un supresor de tumores crucial.
- PTEN actúa como un antagonista clave de la vía de señalización de la fosfoinositida-3 quinasa (PI3K), que a menudo está desregulada en el cáncer.
Objetivo del estudio:
- Para identificar y caracterizar nuevas variantes funcionales de PTEN.
- Investigar las posibles aplicaciones terapéuticas de una variante de PTEN recientemente identificada.
Principales métodos:
- Identificación de una variante de traducción utilizando sitios de inicio de traducción alternativos.
- Análisis bioquímicos para determinar la actividad de la lipida fosfatasa.
- Estudios in vitro e in vivo para evaluar los efectos antitumorales.
Principales resultados:
- Se identificó una variante de 576-aminoácido, PTEN-Long, que se originó en un sitio de inicio de traducción alternativo aguas arriba.
- PTEN-Long es una fosfatasa lipídica secretada y permeable a la membrana capaz de entrar en otras células.
- El PTEN-Long exógeno antagonizó efectivamente la señalización de PI3K e indujo la muerte de las células tumorales tanto en modelos in vitro como in vivo.
Conclusiones:
- PTEN-Long representa una nueva variante funcional del supresor de tumores PTEN.
- Su capacidad para ser internalizada por las células e inhibir la señalización de PI3K sugiere un potencial terapéutico.
- La restauración de la proteína PTEN funcional a través de PTEN-Long podría ser una estrategia viable para el tratamiento del cáncer.
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