title: Wig-1, a novel regulator of N-Myc mRNA and N-Myc-driven tumor growth.
abstract: Wig-1 is a transcriptional target of the p53 tumor suppressor and encodes an mRNA stability-regulating protein. We show here that Wig-1 knockdown causes a dramatic inhibition of N-Myc expression and triggers differentiation in neuroblastoma cells carrying amplified N-Myc. Transient Wig-1 knockdown significantly delays development of N-Myc-driven tumors in mice. We also show that N-Myc expression is induced upon moderate p53-activating stress, suggesting a role of the p53-Wig-1-N-Myc axis in promoting cell cycle re-entry upon p53-induced cell cycle arrest and DNA repair. Moreover, our findings raise possibilities for the improved treatment of poor prognosis neuroblastomas that carry amplified N-Myc.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE-171 76, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Vilborg
authors.forename: C
authors.initials: C
authors.lastname: Bersani
authors.forename: M
authors.initials: M
authors.lastname: Wickström
authors.forename: L
authors.initials: L
authors.lastname: Segerström
authors.forename: P
authors.initials: P
authors.lastname: Kogner
authors.forename: K G
authors.initials: KG
authors.lastname: Wiman
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D004260:DNA Repair; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C436503:ZMAT3 protein, human