title: CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.
abstract: Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway), as the only gene whose expression was affected by the translocation. CDC91L1 was amplified and overexpressed in about one-third of bladder cancer cell lines and primary tumors, as well as in oncogenic uroepithelial cells transformed with human papillomavirus (HPV) E7. Forced overexpression of CDC91L1 malignantly transformed NIH3T3 cells in vitro and in vivo. Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells. Our findings suggest that CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Division of Head and Neck Cancer Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Guo
authors.forename: Jürgen F
authors.initials: JF
authors.lastname: Linn
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Anzick
authors.forename: Claus F
authors.initials: CF
authors.lastname: Eisenberger
authors.forename: Sarel
authors.initials: S
authors.lastname: Halachmi
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Alexey
authors.initials: A
authors.lastname: Fomenkov
authors.forename: Mohammad Obaidul
authors.initials: MO
authors.lastname: Hoque
authors.forename: Kenji
authors.initials: K
authors.lastname: Okami
authors.forename: Gabriel
authors.initials: G
authors.lastname: Steiner
authors.forename: James M
authors.initials: JM
authors.lastname: Engles
authors.forename: Motonabu
authors.initials: M
authors.lastname: Osada
authors.forename: Chulso
authors.initials: C
authors.lastname: Moon
authors.forename: Edward
authors.initials: E
authors.lastname: Ratovitski
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
mesh_terms: D000818:Animals; D002890:Chromosomes, Human, Pair 20; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009857:Oncogenes; D014178:Translocation, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*