PLoS ONE (Jan 2014)

Phosphocaveolin-1 enforces tumor growth and chemoresistance in rhabdomyosarcoma.

  • Fiorella Faggi,
  • Stefania Mitola,
  • Guglielmo Sorci,
  • Francesca Riuzzi,
  • Rosario Donato,
  • Silvia Codenotti,
  • Pietro Luigi Poliani,
  • Manuela Cominelli,
  • Raffaella Vescovi,
  • Stefania Rossi,
  • Stefano Calza,
  • Marina Colombi,
  • Fabio Penna,
  • Paola Costelli,
  • Ilaria Perini,
  • Maurilio Sampaolesi,
  • Eugenio Monti,
  • Alessandro Fanzani

DOI
https://doi.org/10.1371/journal.pone.0084618
Journal volume & issue
Vol. 9, no. 1
p. e84618

Abstract

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Caveolin-1 (Cav-1) can ambiguously behave as either tumor suppressor or oncogene depending on its phosphorylation state and the type of cancer. In this study we show that Cav-1 was phosphorylated on tyrosine 14 (pCav-1) by Src-kinase family members in various human cell lines and primary mouse cultures of rhabdomyosarcoma (RMS), the most frequent soft-tissue sarcoma affecting childhood. Cav-1 overexpression in the human embryonal RD or alveolar RH30 cells yielded increased pCav-1 levels and reinforced the phosphorylation state of either ERK or AKT kinase, respectively, in turn enhancing in vitro cell proliferation, migration, invasiveness and chemoresistance. In contrast, reducing the pCav-1 levels by administration of a Src-kinase inhibitor or through targeted Cav-1 silencing counteracted the malignant in vitro phenotype of RMS cells. Consistent with these results, xenotransplantation of Cav-1 overexpressing RD cells into nude mice resulted in substantial tumor growth in comparison to control cells. Taken together, these data point to pCav-1 as an important and therapeutically valuable target for overcoming the progression and multidrug resistance of RMS.