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La pantalla de reutilización de medicamentos identifica el tiostreptón como un nuevo regulador del supresor tumoral

Rossella De Florian Fania¹, Serena Maiocchi^1,2, Raffaella Klima²

¹Department of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy.

|August 28, 2025

Resumen

Los investigadores identificaron el tiostreptón como un fármaco que aumenta los niveles del supresor tumoral DAB2IP (Disabled-2 Interacting Protein). La reactivación de DAB2IP puede ser una nueva estrategia para el tratamiento de cánceres agresivos.

Área de la Ciencia:

En el campo de la oncología
Biología molecular
Descubrimiento de drogas

Sus antecedentes:

DAB2IP (Disabled-2 Interacting Protein) es un supresor tumoral que inhibe las vías oncogénicas.
La pérdida de DAB2IP promueve la metástasis del cáncer y la resistencia a la terapia.
La reactivación de DAB2IP es prometedora para reducir la agresividad del cáncer.

Objetivo del estudio:

Para detectar las drogas que aumentan los niveles de proteína DAB2IP.
Identificar nuevas estrategias terapéuticas dirigidas a DAB2IP en el cáncer.

Principales métodos:

Utilizó la edición de genes CRISPR / Cas9 para crear modelos de células de cáncer de próstata con DAB2IP fusionado con una etiqueta HiBiT.
Se utiliza la detección basada en la luminiscencia para la medición sensible y cuantitativa de los niveles de proteína DAB2IP.
Examinó una biblioteca de drogas para identificar compuestos que regulan el DAB2IP.

Principales resultados:

Se identificaron varios fármacos capaces de aumentar los niveles de proteína DAB2IP.
Se centró en el tiostreptón, un antibiótico natural, y confirmó su capacidad para elevar la DAB2IP.
Se ha demostrado que los efectos anticancerígenos del tiostreptón disminuyen en ausencia de DAB2IP, lo que indica que la regulación al alza de DAB2IP contribuye a su eficacia.

Conclusiones:

La actividad antitumoral del tiostreptón está, en parte, mediada por la regulación al alza de DAB2IP.
DAB2IP representa un nuevo objetivo molecular para los efectos anticancerígenos del tiostreptón.
Se justifica un mayor desarrollo del tiostreptón para el tratamiento del cáncer sólido.

Palabras clave:

AIP1 (en inglés)CRISPR-Cas9 también En el caso de los vehículos de motor HiBiT (en inglés)Ras-GAP (en inglés)cribado de alto rendimiento Cáncer de próstata Etiquetado de las proteínas genes supresores de tumores

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