B-cell clonogenic activity of HIV-1 p17 variants is driven by PAR1-mediated EGF transactivation
Cinzia Giagulli, Francesca Caccuri, Simone Zorzan, Antonella Bugatti, Alberto Zani, Federica Filippini, Ekta Manocha, Pasqualina D'Ursi, Alessandro Orro, Riccardo Dolcetti, Arnaldo Caruso
CANCER GENE THERAPY | SPRINGERNATURE | Published : 2020
Combined antiretroviral therapy (cART) for HIV-1 dramatically slows disease progression among HIV+ individuals. Currently, lymphoma represents the main cause of death among HIV-1-infected patients. Detection of p17 variants (vp17s) endowed with B-cell clonogenic activity in HIV-1-seropositive patients with lymphoma suggests their possible role in lymphomagenesis. Here, we demonstrate that the clonogenic activity of vp17s is mediated by their binding to PAR1 and to PAR1-mediated EGFR transactivation through Gq protein. The entire vp17s-triggered clonogenic process is MMPs dependent. Moreover, phosphoproteomic and bioinformatic analysis highlighted the crucial role of EGFR/PI3K/Akt pathway in ..View full abstract
Awarded by Associazione Italiana per la Ricerca sul Cancro
This study was supported by Associazione Italiana per la Ricerca sul Cancro; Grant number: 20108 to Arnaldo Caruso and 14287 to Riccardo Dolcetti.