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CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer

Nature Medicine volume 10, pages 374–381 (2004)Cite this article

A Corrigendum to this article was published on 01 October 2004

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.

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Figure 1: Identification of germline translocation breakpoint and affected genes in proband.
Figure 2: FISH analysis of P1 region and expression status of candidate genes in bladder cancer cell lines and tissues.
Figure 3: Oncogenic assays for CDC91L1 and PINH.
Figure 4: Frequency of altered CDC91L1 expression in primary bladder cancer tissues.
Figure 5: Overexpression of GPI-anchored proteins in bladder cancer cell lines, and sensitivity to proaerolysin.

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Acknowledgements

We thank F. Wu, N. Vij, K. Irani and A. Haile for technical support and Ras-transformed NIH3T3 cells. This work was supported by grant 5P01CA77664 from the National Cancer Institute, and by a grant from the Flight Attendant Medical Research Institute.

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Authors and Affiliations

  1. Department of Otolaryngology, Division of Head and Neck Cancer Research, Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Zhongmin Guo, Jürgen F. Linn, Guojun Wu, Claus F Eisenberger, Sarel Halachmi, Yoram Cohen, Mohammad Obaidul Hoque, Kenji Okami, Gabriel Steiner, James M Engles, Motonabu Osada, Chulso Moon, Edward Ratovitski, David Sidransky & Barry Trink

  2. Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Sarah L Anzick, Jeffrey M Trent & Paul S Meltzer

  3. Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Alexey Fomenkov & Edward Ratovitski

  4. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    William H Westra

  5. Department of Epidemiology & Biostatistics, Department of Urology, University Medical Centre, Nijmegen, 6500 HB, The Netherlands

    Lambertus A Kiemeney

  6. Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins Hospital Medical Institutions, Baltimore, 21205, Maryland, USA

    Mark P Schoenberg

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Correspondence to David Sidransky or Barry Trink.

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Guo, Z., Linn, J., Wu, G. et al. CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer. Nat Med 10, 374–381 (2004). https://doi.org/10.1038/nm1010

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