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Endo/exo-proteolysis in neoplastic progression and metastasis

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Abstract

Biological control of individual cells, organs, and organisms is achieved through interplay of a host of specific interactions that involve various peptidic molecules as modulators or effectors. In tumor cells, these processes may result in uncontrolled growth as a consequence of autocrine and/or paracrine actions. In recent years, growing evidence has accumulated for the important role of proprotein convertases (PCs) and peptide α-amidation enzymes in these processes. The widespread belief that these enzymes are involved in the major features of tumor progression, namely, invasiveness and metastasis, has taken place because of their capacity to process and activate many protein precursors involved in the neoplastic progression and metastasis. This includes degrading extracellular matrix proteases, growth promoting factors, and adhesion molecules. Usually, when the processing of these precursor proteins is achieved by one or more of the known PC family members within the general motif (K/R)-(X) n -(K/R)↓, where n=0, 2, 4, or 6, and X, any amino acid except Cys, the accomplishment of the maturation of these molecules is attained by various posttranslational modifications, including the carboxy-terminal α-amidation. This review article summarizes recent findings on the role of these enzymatic systems in multiple cellular functions that impact on the invasive/metastatic potential of cancer cells and highlight the potential use of their inhibitors in the treatment of multiple cancers.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie Expérimentale et Clinique, INSERM U 716, Institut de Génétique Moléculaire, Paris, France

    Abdel-Majid Khatib

  2. Regional Protein Chemistry Centre, Diseases of Ageing Unit, Ottawa Health Research Institute, Loeb Building, 725 Parkdale Ave., Ottawa, Ontario, K1Y 4E9, Canada

    Abdel-Majid Khatib

  3. Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Daniel Bassi & Andres J. P. Klein-Szanto

  4. INSERM U143, 84 Rue Général Leclerc, 94276, Le Kremlin-Bicêtre, France

    Geraldine Siegfried

  5. Laboratoire de Cancérologie Expérimentale, INSERM E359, IFR Jean-Roche, Faculté de médecine Nord, Marseille, France

    L’Houcine Ouafik

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  1. Abdel-Majid Khatib
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  2. Daniel Bassi
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Khatib, AM., Bassi, D., Siegfried, G. et al. Endo/exo-proteolysis in neoplastic progression and metastasis. J Mol Med 83, 856–864 (2005). https://doi.org/10.1007/s00109-005-0692-y

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