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Una función metabólica de las fusiones del gen FGFR3-TACC3 en el cáncer

Véronique Frattini¹, Stefano M Pagnotta^1,2, Tala¹

¹Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.

|January 12, 2018

Resumen

Las fusiones de genes FGFR3-TACC3 (F3-T3) impulsan el cáncer mediante la activación de la respiración mitocondrial. Dirigirse a esta vía metabólica ofrece una nueva estrategia terapéutica para los tumores F3-T3 positivos.

Área de la Ciencia:

En el campo de la oncología
Biología molecular
Metabolismo del cáncer

Sus antecedentes:

Las translocaciones cromosómicas que crean fusiones de genes oncogénicos son objetivos clave en la terapia del cáncer.
Las fusiones FGFR3-TACC3 (F3-T3) son factores oncogénicos que se encuentran en varios tipos de cáncer, incluido el glioblastoma.
Las vías de señalización aguas abajo de las fusiones F3-T3 siguen siendo en gran medida desconocidas.

Objetivo del estudio:

Para aclarar las vías de señalización oncogénicas activadas por las fusiones F3-T3.
Investigar el papel de la función mitocondrial en la tumorigénesis impulsada por F3-T3.
Identificar las posibles vulnerabilidades terapéuticas en los cánceres F3-T3 positivos.

Principales métodos:

Perfiles de transcripción de tumores humanos con fusiones F3-T3.
Análisis de la función mitocondrial y el metabolismo oxidativo.
Investigación del eje de señalización F3-T3-PIN4 y sus efectos posteriores.

Principales resultados:

Las fusiones F3-T3 están asociadas con subgrupos de transcripción caracterizados por funciones mitocondriales activadas.
F3-T3 activa la fosforilación oxidativa y la biogénesis mitocondrial, confiriendo sensibilidad a los inhibidores metabólicos.
El eje F3-T3-PIN4 promueve la biogénesis del peroxisoma y la síntesis de proteínas, convergiendo en PGC1α a través de especies reactivas de oxígeno.

Conclusiones:

Los tumores F3-T3 positivos exhiben una fuerte dependencia de la respiración mitocondrial para el crecimiento.
La activación del metabolismo mitocondrial mediada por F3-T3 representa una oportunidad terapéutica significativa.
Comprender el circuito metabólico de las fusiones F3-T3 proporciona información sobre el desarrollo y el tratamiento del cáncer.

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