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

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

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16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)585-602
Number of pages18
JournalLaboratory Investigation
Volume95
Issue number6
DOIs
StatePublished - Jun 28 2015

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Faggi, F., Chiarelli, N., Colombi, M., Mitola, S., Ronca, R., Madaro, L., Bouche, M., Poliani, P. L., Vezzoli, M., Longhena, F., Monti, E., Salani, B., Maggi, D., Keller, C., & Fanzani, A. (2015). Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma. Laboratory Investigation, 95(6), 585-602. https://doi.org/10.1038/labinvest.2015.45