CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.
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.
Guo
Zhongmin
Z
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.
Linn
Jürgen F
JF
Wu
Guojun
G
Anzick
Sarah L
SL
Eisenberger
Claus F
CF
Halachmi
Sarel
S
Cohen
Yoram
Y
Fomenkov
Alexey
A
Hoque
Mohammad Obaidul
MO
Okami
Kenji
K
Steiner
Gabriel
G
Engles
James M
JM
Osada
Motonabu
M
Moon
Chulso
C
Ratovitski
Edward
E
Trent
Jeffrey M
JM
Meltzer
Paul S
PS
Westra
William H
WH
Kiemeney
Lambertus A
LA
Schoenberg
Mark P
MP
Sidransky
David
D
Trink
Barry
B
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*