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La UDP-glucosa acelera la descomposición del ARNm SNAI1 y dificulta la metástasis del cáncer de pulmón

Xiongjun Wang^1,2,3, Ruilong Liu^1,2, Wencheng Zhu¹

¹State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.

|June 28, 2019

Resumen

La UDP-glucosa 6- deshidrogenasa (UGDH) promueve la metástasis del cáncer de pulmón mediante la estabilización del ARNm SNAI1. Este proceso implica la fosforilación de UGDH, mejorando la migración de las células tumorales y prediciendo un mal pronóstico para el paciente.

Área de la Ciencia:

En el campo de la oncología
Biología del cáncer
Metabolismo molecular

Sus antecedentes:

La metástasis del cáncer es una causa importante de muertes relacionadas con el cáncer, impulsada por la reprogramación metabólica.
El papel de las alteraciones metabólicas en la migración y metástasis de las células tumorales no se comprende completamente.
La UDP-glucosa 6- deshidrogenasa (UGDH) es una enzima en la vía del ácido urónico.

Objetivo del estudio:

Investigar el papel de la UGDH en la migración y metástasis de las células del cáncer de pulmón.
Para aclarar el mecanismo molecular por el cual UGDH influye en el comportamiento de las células tumorales.
Determinar la importancia clínica de la actividad de la UGDH en pacientes con cáncer de pulmón.

Principales métodos:

Se ha investigado la fosforilación de UGDH en la tirosina 473 en células de cáncer de pulmón.
Se examinó la interacción entre la UGDH fosforilada, el antígeno Hu R (HuR) y el ARNm SNAI1.
Se evaluó el impacto de la actividad de la UGDH en la transición epitelio-mesenquimal (EMT) y la migración de las células tumorales.
Niveles de fosforilación de UGDH correlacionados con el pronóstico del paciente y la recurrencia metastásica.

Principales resultados:

La activación del EGFR conduce a la fosforilación de UGDH en la tirosina 473 en las células de cáncer de pulmón.
La UGDH fosforilada interactúa con la HuR, mejorando la estabilidad del ARNm SNAI1.
Esta estabilización promueve la producción de SNAIL, iniciando la EMT y aumentando la migración y la metástasis de las células tumorales.
La fosforilación de UGDH en tirosina 473 está asociada con la recurrencia metastásica y un mal pronóstico en pacientes con cáncer de pulmón.

Conclusiones:

La UGDH promueve la metástasis del cáncer de pulmón al aumentar la estabilidad del ARNm SNAI1 a través de la fosforilación.
La UDP-glucosa juega un papel supresor del tumor en la metástasis del cáncer de pulmón.
Dirigirse al eje UGDH-HuR-SNAI1 puede ofrecer estrategias terapéuticas para la metástasis del cáncer de pulmón.

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