title: Phosphoinositide 3-kinase p85beta regulates invadopodium formation.
abstract: 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 p85β, a regulatory subunit of phosphoinositide-3-kinase, markedly increases in advanced carcinoma, but its mode of action is unknown. We postulated that p85β might facilitate cell invasion. We show that p85β localized at cell adhesions in complex with focal adhesion kinase and enhanced stability and maturation of cell adhesions. In addition, p85β induced development at cell adhesions of an F-actin core that extended several microns into the cell z-axis resembling the skeleton of invadopodia. p85β lead to F-actin polymerization at cell adhesions by recruiting active Cdc42/Rac at these structures. In accordance with p85β function in invadopodium-like formation, p85β levels increased in metastatic melanoma and p85β depletion reduced invadopodium formation and invasion. These results show that p85β enhances invasion by inducing cell adhesion development into invadopodia-like structures explaining the metastatic potential of tumors with increased p85β levels.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Cariaga-Martínez
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cortés
authors.affiliation: Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: García
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Pérez-García
authors.affiliation: Biomarkers Laboratory, Division of Oncology, Center for Applied Biomedical Research (CIMA), University of Navarra, Pamplona E-31008, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Pajares
authors.affiliation: Pathology Department, Hospital Clinic of Navarra, University of Navarra, Pamplona, E-31008, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Idoate
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Redondo-Muñóz
authors.affiliation: Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: Inés M
authors.initials: IM
authors.lastname: Antón
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid E-28049, Spain acarrera@cnb.csic.es.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Carrera
keywords: cell adhesion; invadopodium; invasion; metastasis; p85β