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La OTUD4 regula la progresión del cáncer de páncreas a través del eje Hippo/YAP

Shuaike Qu¹, Zhihao Liu¹, Beibei Wang²

¹Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110000, Liaoning Province, PR China.

Neoplasia (New York, N.Y.)

|February 13, 2026

Resumen

La proteína que contiene el dominio OTU 4 (OTUD4) promueve la progresión del adenocarcinoma de páncreas (PAAD) al estabilizar la proteína asociada a Yes (YAP). La depleción de OTUD4 reduce la actividad Hippo/YAP y dificulta el crecimiento del PAAD, lo que sugiere que OTUD4 es un objetivo terapéutico.

Área de la Ciencia:

Oncología
Biología Molecular
Bioquímica

Sus antecedentes:

La vía de señalización Hippo/proteína asociada a Yes (YAP) se sobreactiva frecuentemente en el adenocarcinoma de páncreas (PAAD).
La estabilidad de las proteínas, particularmente la de YAP, está regulada por la ubiquitinación y juega un papel crítico en la señalización Hippo y el PAAD.
Los mecanismos precisos que vinculan la estabilidad de la proteína YAP con la actividad de Hippo en el PAAD siguen sin entenderse completamente.

Objetivo del estudio:

Elucidar el papel de la modificación por ubiquitina en la señalización Hippo/YAP dentro del adenocarcinoma de páncreas.
Identificar los efectores clave que regulan la estabilidad de la proteína YAP y la actividad de la vía Hippo en el PAAD.
Investigar la proteína que contiene el dominio OTU 4 (OTUD4) como un objetivo terapéutico potencial en el PAAD.

Principales métodos:

Se emplearon el análisis de enriquecimiento de conjuntos de genes (GSEA) y el cribado por ARN de interferencia (siRNA).
Se realizaron estudios de interacción de proteínas, incluida la co-inmunoprecipitación.
Se analizaron datos de expresión de tejidos de PAAD y se realizaron ensayos funcionales.

Principales resultados:

La proteína que contiene el dominio OTU 4 (OTUD4) se identificó como un efector crucial de la señalización Hippo en el PAAD.
La alta expresión de OTUD4 en tejidos de PAAD se correlacionó con la expresión de genes diana de Hippo.
La depleción de OTUD4 inhibió significativamente la actividad del eje Hippo/YAP y obstaculizó la progresión del PAAD.
Se encontró que OTUD4 interactúa con YAP, promoviendo su poliquitinación K48-ligada y la posterior degradación.

Conclusiones:

OTUD4 regula la señalización Hippo/YAP controlando la estabilidad de la proteína YAP en el adenocarcinoma de páncreas.
La targeting de OTUD4 presenta una estrategia terapéutica potencial para tratar el PAAD.
Este estudio descubre un nuevo mecanismo regulatorio que involucra a OTUD4 en la progresión del PAAD.

Palabras clave:

eje Hippo/YAP OTUD4 adenocarcinoma de páncreas ubiquitina

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