title: Caveolin-1 is down-regulated in alveolar rhabdomyosarcomas and negatively regulates tumor growth.
abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with histological variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of less than 30%. Caveolin-1 (CAV1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signaling. In the present study we report that compared to other forms of rhabdomyosarcoma (RMS) CAV1 expression is either undetectable or very low in ARMS cell lines and tumor samples. DNA methylation analysis of the promoter region and azacytidine-induced re-expression suggest the involvement of epigenetic mechanisms in the silencing of CAV1. Reintroduction of CAV1 in three of these cell lines impairs their clonogenic capacity and promotes features of muscular differentiation. In vitro, CAV1-expressing cells show high expression of Caveolin-3 (CAV3), a muscular differentiation marker. Blockade of MAPK signaling is also observed. In vivo, CAV1-expressing xenografts show growth delay, features of muscular differentiation and increased cell death. In summary, our results suggest that CAV1 could function as a potent tumor suppressor in ARMS tumors. Inhibition of CAV1 function therefore, could contribute to aberrant cell proliferation, leading to ARMS development.
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Huertas-Martínez
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rello-Varona
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Herrero-Martín
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Barrau
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: García-Monclús
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sáinz-Jaspeado
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Lagares-Tena
authors.affiliation: Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Barcelona, Spain.
authors.forename: Yaiza
authors.initials: Y
authors.lastname: Núñez-Álvarez
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Deu, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mateo-Lozano
authors.affiliation: Developmental Tumor Biology Laboratory, Hospital Sant Joan de Deu, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Mora
authors.affiliation: Biomedical Research Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Roma
authors.affiliation: Biomedical Research Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Toran
authors.affiliation: Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L' Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Moran
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: López-Alemany
authors.affiliation: Biomedical Research Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Gallego
authors.affiliation: Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L' Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Barcelona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Peinado
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Xavier García
authors.initials: XG
authors.lastname: Del Muro
authors.affiliation: Sarcoma research group, Molecular Oncology Lab, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Tirado
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051242:Caveolin 1