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From Rous sarcoma virus to plasminogen activator, src oncogene and cancer management

Oncogene volume 30, pages 3003–3010 (2011)Cite this article

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Abstract

Plasminogen activator (PLAU) is a serine protease that converts plasminogen to plasmin, a general protease, which promotes fibrinolysis and degradation of extracellular matrix. PLAU was reported in 1970s as one of the robustly induced enzymatic activities in Rous sarcoma virus (RSV)-transformed chicken cells. More than three decades later, with the completion of the sequencing of the chicken genome and the subsequent availability of Affymetrix GeneChip genome arrays, several laboratories have surveyed the transcriptional program affected by the RSV transformation. Interestingly, the PLAU gene was shown to be the most highly upregulated transcript. The induction of PLAU was a transformation-dependent process because viruses with deleted Src gene did not induce the transcription of the PLAU gene. Both Src and PLAU genes are associated with and contribute to the complex phenotype of human cancer. Although the activity and structures of these two enzymes are well characterized, the precise molecular function of these gene products in signaling networks is still not fully understood. Yet, the knowledge of their association with cancer is already translated into the clinical setting. Src kinase inhibitors are being tested in clinical trials of cancer therapy, and PLAU gene and its inhibitor have been included as biomarkers with strong prognostic and therapeutic predictive values. This vignette reviews the history of PLAU and Src discovery, and illuminates the complexity of their relationship, but also points to their emerging impact on public health.

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Acknowledgements

Special thanks are to Mario Gimona for translating the 1925 publication of Fischer from German to English and for valuable comments on the text, Bethany Antos and Lee Hiltzik from the Rockefeller Archive Center for the photographs and information about 1979 Rous Centennial. Kathy Sheridan and Peter K Vogt are thanked for valuable comments on the early version of the manuscript, and Angelika Barnekow for a fruitful collaboration and permission to mention our unpublished data. I am grateful to my PhD mentors Ed Reich and Wolf-Dieter Schleuning, my senior colleagues Mary Rifkin, Tony Cerami, Sidney Strickland, Jean-Dominique Vassalli, Yoshi Nagamine, Michael W Young, and my peers Michael E Greenberg, Michael Yamin and Ned Waller for their guidance throughout my Rockefeller tenure. My postdoctoral mentor, the late Hidesaburo Hanafusa, is remembered with warmth. This work was supported by PA Breast Cancer Coalition grants and by Geisinger Clinic.

This mini-review is not meant to comprehensively discuss all relevant publications. The references are intentionally selective and the author apologizes for omission of many pertinent publications, and for the myopic focus of this article.

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  1. Laboratory of Signal Transduction and Proteomic Profiling, Weis Center for Research, Geisinger Clinic, Danville, PA, USA

    M Sudol

  2. Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA

    M Sudol

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Sudol, M. From Rous sarcoma virus to plasminogen activator, src oncogene and cancer management. Oncogene 30, 3003–3010 (2011). https://doi.org/10.1038/onc.2011.38

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