Phosphocaveolin-1 enforces tumor growth and chemoresistance in rhabdomyosarcoma.

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 in the human embryonal RD or alveolar RH30 cells yielded increased pCav-1 levels and reinforced the phosphorylation state of either ERK or AKT kinase, 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.

• Authors: Fiorella Faggi, Stefania Mitola, Guglielmo Sorci, Francesca Riuzzi, Rosario Donato, Silvia Codenotti, Pietro Luigi Poliani, Manuela Cominelli, Raffaella Vescovi, Stefania Rossi, Stefano Calza, Marina Colombi, Fabio Penna, Paola Costelli, Ilaria Perini, Maurilio Sampaolesi, Eugenio Monti, Alessandro Fanzani
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e84618 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24427291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caveolin 1
• Protein Kinase Inhibitors
• src-Family Kinases
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Caveolin 1 (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Disease Models, Animal
• Drug Resistance, Neoplasm (genetics)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Gene Expression
• Heterografts
• Humans
• Mice
• Phosphorylation
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (metabolism)
• Rhabdomyosarcoma (genetics, metabolism, pathology)
• Tumor Burden (genetics)
• src-Family Kinases (metabolism)