Research Papers:

The proprotein convertase furin is required to maintain viability of alveolar rhabdomyosarcoma cells

Patricia Jaaks, Gianmarco Meier, Nagjie Alijaj, Eva Brack, Peter Bode, Ewa Koscielniak, Marco Wachtel, Beat W. Schäfer and Michele Bernasconi _

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Oncotarget. 2016; 7:76743-76755. https://doi.org/10.18632/oncotarget.11648

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Patricia Jaaks1, Gianmarco Meier1, Nagjie Alijaj1, Eva Brack1, Peter Bode2, Ewa Koscielniak3, Marco Wachtel1, Beat W. Schäfer1, Michele Bernasconi1

1Department of Oncology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland

2Department of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland

3Department of Oncology/Hematology/Immunology, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany

Correspondence to:

Michele Bernasconi, email: [email protected]

Keywords: furin, proprotein convertases, rhabdomyosarcoma, apoptosis, IGF1R

Received: February 10, 2016    Accepted: August 09, 2016    Published: August 27, 2016


Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Success of current therapies is still limited and outcome is particularly poor for metastatic alveolar rhabdomyosarcoma (aRMS). We previously identified the proprotein convertase furin as potential target for specific drug delivery with RMS-homing peptides. Furin is a protease that converts inactive precursor proteins into bioactive proteins and peptides. In this study, we investigate the biological role of furin in aRMS progression in vitro and in vivo. Furin expression was confirmed in over 86% RMS biopsies in a tissue microarray (n=89). Inducible furin silencing in vitro led to significant impairment of cell viability and proliferation in all investigated aRMS cell lines, but not in MRC5 fibroblasts. Furthermore, the aRMS cell lines Rh3 and Rh4 revealed to be very sensitive to furin silencing, undergoing caspase-dependent cell death. Notably, furin silencing in vivo led to complete remission of established Rh4 tumors and to delayed growth in Rh30 tumors. Taken together, these findings identify furin as an important factor for aRMS progression and survival. Thus, we propose furin as a novel therapeutic target for treatment of aRMS.

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