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La proteasa HapA se dirige a PAR-1/2 para modular la señalización de ERK y reducir la viabilidad de las células
David Tena-Chaves1, Inês Pontes-Gomes1, José Ángel Palomeque1
1Centro de Investigación del Cáncer, CSIC and Universidad de Salamanca, Salamanca, Spain.
Cell death discovery
|August 28, 2025
Resumen
Vibrio cholerae
Área de la Ciencia:
- Microbiología
- Biología celular
- Investigación del cáncer
Sus antecedentes:
- Los factores de virulencia de Vibrio cholerae afectan la viabilidad de las células huésped, pero los efectos sobre las células cancerosas no están claros.
- Los componentes bacterianos y los mecanismos que influyen en las células cancerosas son en gran medida desconocidos.
- Investigando mutantes de V. cholerae que carecen de proteínas secretadas en las células del carcinoma.
Objetivo del estudio:
- Investigar los efectos de las proteínas secretadas por V. cholerae en las células cancerosas.
- Identificar los factores bacterianos que influyen en la viabilidad de las células cancerosas.
- Para explorar posibles objetivos terapéuticos para el tratamiento del cáncer.
Principales métodos:
- Estudió mutantes de V. cholerae que carecen de proteínas secretadas.
- Analizó los efectos de los componentes bacterianos en las células del carcinoma.
- Investigó la escisión de los receptores activados por proteasa (PAR) y las vías de señalización aguas abajo.
Principales resultados:
- Se ha identificado a la hemaglutinina zinc-metaloproteasa (HapA) como un factor clave que reduce la viabilidad de las células cancerosas.
- HapA divide los receptores 1 y 2 activados por la proteasa (PAR-1/2) en las células cancerosas epiteliales.
- La escisión mediada por HapA activa transitoriamente las cinasas MEK y ERK, iniciando la caspasa 7 y la apoptosis.
Conclusiones:
- La HapA es un factor de virulencia significativo que afecta la viabilidad de las células cancerosas.
- HapA tiene como objetivo el PAR-1/2 humano, modulando la señalización MEK-ERK.
- La escisión selectiva de HapA de PAR-1/2 ofrece potencial para nuevas terapias contra el cáncer.
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