Detalle Publicación


Phosphoinositide 3-kinase p85beta regulates invadopodium formation

Autores: Cariaga-Martínez, A. E.; Cortés, I.; García, E.; Pérez-García, V.; Pajares Villandiego, María José; Idoate Gastearena, Miguel Ángel; Redondo-Muñoz, J.; Antón, I. M.; Carrera, A. C.
Título de la revista: BIOLOGY OPEN
ISSN: 2046-6390
Volumen: 3
Número: 10
Páginas: 924 - 936
Fecha de publicación: 2014
The acquisition of invasiveness is characteristic of tumor progression. Numerous genetic changes are associated with metastasis, but the mechanism by which a cell becomes invasive remains unclear. Expression of p85ß, a regulatory subunit of phosphoinositide-3-kinase, markedly increases in advanced carcinoma, but its mode of action is unknown. We postulated that p85ß might facilitate cell invasion. We show that p85ß localized at cell adhesions in complex with focal adhesion kinase and enhanced stability and maturation of cell adhesions. In addition, p85ß induced development at cell adhesions of an F-actin core that extended several microns into the cell z-axis resembling the skeleton of invadopodia. p85ß lead to F-actin polymerization at cell adhesions by recruiting active Cdc42/Rac at these structures. In accordance with p85ß function in invadopodium-like formation, p85ß levels increased in metastatic melanoma and p85ß depletion reduced invadopodium formation and invasion. These results show that p85ß enhances invasion by inducing cell adhesion development into invadopodia-like structures explaining the metastatic potential of tumors with increased p85ß levels.