title: 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.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Faggi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mitola
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Sorci
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Riuzzi
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Codenotti
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Pietro Luigi
authors.initials: PL
authors.lastname: Poliani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cominelli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Vescovi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Calza
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.affiliation: Department of Experimental Medicine and Oncology, University of Torino, Torino, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.affiliation: Department of Experimental Medicine and Oncology, University of Torino, Torino, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Costelli
authors.affiliation: Stem Cell Research Institute, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Perini
authors.affiliation: Stem Cell Research Institute, University Hospital Gasthuisberg, Leuven, Belgium ; Human Anatomy Section, University of Pavia, Pavia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Sampaolesi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy ; Interuniversity Institute of Myology (IIM), Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fanzani
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D047368:Tumor Burden / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D047428:Protein Kinase Inhibitors; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases