Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma

• DOI: 10.1038/labinvest.2015.45
• Publication Date: 2015-03-30T12:38:26Z
• Authors: Fiorella Faggi; Nicola Chiarelli; Marina Colombi; Stefania Mitola; Roberto Ronca; Luca Madaro; Marina Bouche; Pietro L Poliani; Marika Vezzoli; Francesca Longhena; Eugenio Monti; Barbara Salani; Davide Maggi; Charles Keller; Alessandro Fanzani
• Keywords: 0301 basic medicine; Satellite Cells, Skeletal Muscle; proliferation; Caveolin 1; Down-Regulation; migration; rhabdomyosarcoma; Cavin-1; Caveolin-1; proliferation; migration.; Cavin-1; Mice; 03 medical and health sciences; Animals; Caveolin 1; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cells, Cultured; Down-Regulation; Gene Knockdown Techniques; Humans; Membrane Proteins; Mice; RNA-Binding Proteins; Rhabdomyosarcoma; Satellite Cells, Skeletal Muscle; 2734; Cell Biology; Molecular Biology; Medicine (all); Caveolin-1; Cell Movement; Cell Line, Tumor; Rhabdomyosarcoma; Animals; Humans; Cells, Cultured; Cell Proliferation; Membrane Proteins; RNA-Binding Proteins; Cell Differentiation; Gene Knockdown Techniques; rhabdomyosarcoma; rhabdomyosarcoma; RD cells; cavin-1; cav-1

Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typically found in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in the morphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico and in vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouse RMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. In particular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferation of human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during the myogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human RD and RH30 cells led to impairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independent cell growth in soft agar. While the loss of Cavin-1 did not affect the Cav-1 protein levels in RMS cells, Cav-1 overexpression and knockdown triggered a rise or depletion of Cavin-1 protein levels in RD cells, respectively, in turn reflecting on increased or decreased cell proliferation, migration and anchorage-independent cell growth. Collectively, these data indicate that the interaction between Cavin-1 and Cav-1 underlies the cell growth and migration in myogenic tumors.