title: The oncogenic role of the cochaperone Sgt1.
abstract: Sgt1/Sugt1, a cochaperone of Hsp90, is involved in several cellular activities including Cullin E3 ubiqutin ligase activity. The high level of Sgt1 expression in colorectal and gastric tumors suggests that Sgt1 is involved in tumorigenesis. Here, we report that Sgt1 is overexpressed in colon, breast and lung tumor tissues and in Ewing sarcoma and rhabdomyosarcoma xenografts. We also found that Sgt1 heterozygous knockout resulted in suppressed Hras-mediated transformation in vitro and tumor formation in p53(-/-) mouse embryonic fibroblast cells and significantly increased survival of p53(-/-) mice. Moreover, depletion of Sgt1 inhibited the growth of Ewing sarcoma and rhabdomyosarcoma cells and destabilized EWS-FLI1 and PAX3-FOXO1 oncogenic fusion proteins, respectively, which are required for cellular growth. Our results suggest that Sgt1 contributes to cancer development by stabilizing oncoproteins and that Sgt1 is a potential therapeutic target.
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ogi
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuraba
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kitagawa
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: C
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Pathology and Laboratory Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Cynthia
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Department of Pathology and Laboratory Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Arnold
authors.affiliation: Department of Pathology and Laboratory Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ramirez
authors.affiliation: 1] Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA [2] Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, USA [3] Children's Cancer Research Institute, San Antonio, TX, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Houghton
authors.affiliation: 1] Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA [2] Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kitagawa