Understanding fibroblast activation protein (FAP): Substrates, activities, expression and targeting for cancer therapy

Authors

  • Elizabeth J. Hamson,

    1. Molecular Hepatology, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, Australia
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  • Fiona M. Keane,

    1. Molecular Hepatology, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, Australia
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  • Stefan Tholen,

    1. Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany
    2. Faculty of Biology, University of Freiburg, Freiburg, Germany
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  • Oliver Schilling,

    1. Faculty of Biology, University of Freiburg, Freiburg, Germany
    2. BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany
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  • Mark D. Gorrell

    Corresponding author
    1. Molecular Hepatology, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, Australia
    • Correspondence: Associate Professor Mark D. Gorrell, Molecular Hepatology, Centenary Institute and Sydney Medical School, University of Sydney, Locked Bag No. 6, Newtown, NSW 2042, Australia

      E-mail: m.gorrell@centenary.usyd.edu.au

      Fax: +61-2-95656101

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  • Colour Online: See the article online to view Figs. 1–4 in colour.

Abstract

Fibroblast activation protein (FAP) is best known for its heightened expression in tumour stroma. This atypical serine protease has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. FAP expression is difficult to detect in non-diseased adult organs, but is greatly upregulated in sites of tissue remodelling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumours and embryonic tissues. Due to its restricted expression pattern and dual enzymatic activities, FAP is emerging as a unique therapeutic target. However, methods to exploit and target this protease are advancing more rapidly than knowledge of the fundamental biology of FAP. This review highlights this imbalance, emphasising the need to better define the substrate repertoire and expression patterns of FAP to elucidate its role in biological and pathological processes.

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