CDC91LI (PIG-U) is a newly discovered oncogene in human bladder cancer

Zhongmin Guo, Jürgen F. Linn, Guojun Wu, Sarah L. Anzick, Claus F. Eisenberger, Sarel Halachmi, Yoram Cohen, Alexey Fomenkov, Mohammad Obaidul Hoque, Kenji Okami, Gabriel Steiner, James M. Engles, Motonabu Osada, Chulso Moon, Edward Ratovitski, Jeffrey M. Trent, Paul S. Meltzer, William H. Westra, Lambertus A. Kiemeney, Mark P. SchoenbergDavid Sidransky, Barry Trink

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)374-381
Number of pages8
JournalNature Medicine
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Guo, Z., Linn, J. F., Wu, G., Anzick, S. L., Eisenberger, C. F., Halachmi, S., Cohen, Y., Fomenkov, A., Hoque, M. O., Okami, K., Steiner, G., Engles, J. M., Osada, M., Moon, C., Ratovitski, E., Trent, J. M., Meltzer, P. S., Westra, W. H., Kiemeney, L. A., ... Trink, B. (2004). CDC91LI (PIG-U) is a newly discovered oncogene in human bladder cancer. Nature Medicine, 10(4), 374-381. https://doi.org/10.1038/nm1010