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

Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typicallyfound in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in themorphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico andin vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouseRMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. Inparticular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferationof human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during themyogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human embryonal RD and alveolar RH30 cells leads toimpairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independentcell growth in soft agar. Although the loss of Cavin-1 did not affect the Cav-1 protein levels in both RD and RH30 lines, Cav-1 overexpression and knockdown in RD cells triggered a rise or depletion of Cavin-1 protein levels, respectively, in turnreflecting 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 myogenictumors.