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.

Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma / Faggi, Fiorella; Chiarelli, Nicola; Colombi, Marina; Mitola, Stefania; Ronca, Roberto; Madaro, Luca; Bouche', Marina; Poliani, Pietro L; Vezzoli, Marika; Longhena, Francesca; Monti, Eugenio; Salani, Barbara; Maggi, Davide; Keller, Charles; Fanzani, Alessandro. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - STAMPA. - 95:6(2015), pp. 585-602. [10.1038/labinvest.2015.45]

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

MADARO, LUCA;BOUCHE', Marina;
2015

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.
2015
rhabdomyosarcoma; RD cells; cavin-1; cav-1
01 Pubblicazione su rivista::01a Articolo in rivista
Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma / Faggi, Fiorella; Chiarelli, Nicola; Colombi, Marina; Mitola, Stefania; Ronca, Roberto; Madaro, Luca; Bouche', Marina; Poliani, Pietro L; Vezzoli, Marika; Longhena, Francesca; Monti, Eugenio; Salani, Barbara; Maggi, Davide; Keller, Charles; Fanzani, Alessandro. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - STAMPA. - 95:6(2015), pp. 585-602. [10.1038/labinvest.2015.45]
File allegati a questo prodotto
File Dimensione Formato  
Faggi_Cavin-1_2015.pdf

accesso aperto

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.12 MB
Formato Adobe PDF
1.12 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/785701
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 31
  • ???jsp.display-item.citation.isi??? 30
social impact