The Proprotein Convertase Furin Contributes to Rhabdomyosarcoma Malignancy by Promoting Vascularization, Migration and Invasion

• DOI: 10.1371/journal.pone.0161396
• Publication Date: 2016-08-22T17:39:58Z
• Authors: Patricia Jaaks; Valentina D’Aless...; Nicole Grob; Sina Büel; Katarina Hajdin; Beat W. Schäfer; Michele Bernasconi
• Keywords: Furin; Proprotein Convertases

The proprotein convertase (PC) furin cleaves precursor proteins, an important step in the activation of many cancer-associated proteins. Substrates and furin-like PCs play a role proliferation, metastasis invasion. Some them are involved progression pediatric soft tissue sarcoma rhabdomyosarcoma (RMS). In this study, we show that PCs, particular furin, expressed RMS cell lines. To investigate functional generated lines with modulated activity. Silencing or stable inhibition delayed tumor growth Rh30 RD xenografts vivo, was correlated lower microvessel density. Reduced activity also decreased migration invasion abilities vitro, cells diminished processing IGF1R, VEGF-C, PDGF-B MT1-MMP, leading to levels mature Furthermore, found is required for proper IGF signaling cells, as silencing resulted reduced phosphorylation Akt upon IGF1 stimulation. Taken together, our results suggest plays malignant phenotype by activating proteins vascularization,