Caveolin-1 (Cav-1) can ambiguously behave as either tumor suppressor or oncogene depending on its phosphorylation state and the type of cancer. In this study we show that Cav-1 was phosphorylated on tyrosine 14 (pCav-1) by Src-kinase family members in various human cell lines and primary mouse cultures of rhabdomyosarcoma (RMS), the most frequent soft-tissue sarcoma affecting childhood. Cav-1 overexpression yielded increased pCav-1 levels and enforced the phosphorylation state of either ERK or AKT in the human embryonal RD and alveolar RH30 cells, respectively, in turn enhancing in vitro cell proliferation, migration, invasiveness and chemoresistance. In contrast, reducing the pCav-1 levels by administration of a Src-kinase inhibitor or through targeted Cav-1 silencing counteracted the malignant in vitro phenotype of RMS cells. Consistent with these results, xenotransplantation of Cav-1 overexpressing RD cells into nude mice resulted in substantial tumor growth in comparison to control cells. Taken together, these data point to pCav-1 as an important and therapeutically valuable target for overcoming the progression and multidrug resistance of RMS.
Phosphocaveolin-1 enforces tumor growth and chemoresistance in rhabdomyosarcoma / Faggi, Fiorella; Mitola, Stefania Maria Filomena; Sorci, G.; Riuzzi, F.; Donato, R.; Codenotti, S.; Poliani, Pietro Luigi; Cominelli, Manuela; Vescovi, Raffaella; Rossi, Stefania; Calza, Stefano; Colombi, Marina; Penna, F.; Costelli, P.; Perini, I.; Sampaolesi, M.; Monti, Eugenio; Fanzani, Alessandro. - In: PLOS ONE. - ISSN 1932-6203. - 9:1(2014). [10.1371/journal.pone.0084618]
Phosphocaveolin-1 enforces tumor growth and chemoresistance in rhabdomyosarcoma
POLIANI, Pietro Luigi;
2014-01-01
Abstract
Caveolin-1 (Cav-1) can ambiguously behave as either tumor suppressor or oncogene depending on its phosphorylation state and the type of cancer. In this study we show that Cav-1 was phosphorylated on tyrosine 14 (pCav-1) by Src-kinase family members in various human cell lines and primary mouse cultures of rhabdomyosarcoma (RMS), the most frequent soft-tissue sarcoma affecting childhood. Cav-1 overexpression yielded increased pCav-1 levels and enforced the phosphorylation state of either ERK or AKT in the human embryonal RD and alveolar RH30 cells, respectively, in turn enhancing in vitro cell proliferation, migration, invasiveness and chemoresistance. In contrast, reducing the pCav-1 levels by administration of a Src-kinase inhibitor or through targeted Cav-1 silencing counteracted the malignant in vitro phenotype of RMS cells. Consistent with these results, xenotransplantation of Cav-1 overexpressing RD cells into nude mice resulted in substantial tumor growth in comparison to control cells. Taken together, these data point to pCav-1 as an important and therapeutically valuable target for overcoming the progression and multidrug resistance of RMS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
