title: Novel Roles for Staufen1 in Embryonal and Alveolar Rhabdomyosarcoma via c-myc-dependent and -independent events.
abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis. Here, we report for the first time the novel role of Staufen1 in cancer, specifically in rhabdomyosarcoma. We demonstrate that Staufen1 is markedly upregulated in human rhabdomyosarcoma tumours and cell lines as compared to normal skeletal muscle. Moreover, we show that Staufen1 promotes the tumorigenesis of embryonal and alveolar rhabdomyosarcoma subtypes both in cell culture and in animal models. Finally, our data demonstrate that Staufen1 has differential roles in embryonal versus alveolar rhabdomyosarcoma through the control of proliferative and apoptotic pathways, respectively. Together, these results provide the first evidence for Staufen1's direct implication in cancer biology. Accordingly, Staufen1 thus represents a novel target for the development of future therapeutic strategies for rhabdomyosarcoma.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Crawford Parks
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Marcellus
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Langill
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Ravel-Chapuis
authors.affiliation: Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.|Department of Pathology and Laboratory Medicine, University of Ottawa, The Ottawa Hospital and Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Michaud
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.|Department of Surgery, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Kyle N
authors.initials: KN
authors.lastname: Cowan
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Côté
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018232:Rhabdomyosarcoma, Alveolar / Q000378:metabolism* / Q000473:pathology; D018233:Rhabdomyosarcoma, Embryonal / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D003598:Cytoskeletal Proteins; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human