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  • Profilin 1 as a target for cathepsin X activity in tumor cells [Elektronski vir]
    Pečar Fonović, Urša ...
    Cathepsin X has been reported to be a tumor promotion factor in various types of cancer; however, the molecular mechanisms linking its activity with malignant processes are not understood. Here we ... present profilin 1, a known tumor suppressor, as a target for cathepsin X carboxypeptidase activity in prostate cancer PC-3 cells. Profilin 1 co-localizes strongly with cathepsin X intracellularly in the perinuclear area as well as at the plasma membrane. Selective cleavage of C-terminal amino acids was demonstrated on a synthetic octapeptide representing the profilin C-terminal region, and on recombinant profilin 1. Further, intact profilin 1 binds its poly-L-proline ligand clathrin significantly better than it does the truncated one, as shown using cathepsin X specific inhibitor AMS-36 and immunoprecipitation of the profilin 1/clathrin complex. Moreover, the polymerization of actin, which depends also on the binding of poly-L-proline ligands to profilin 1, was promoted by AMS-36 treatment of cells and by siRNA cathepsin X silencing. Our results demonstrate that increased adhesion, migration and invasiveness of tumor cells depend on the inactivation of the tumor suppressive function of profilin 1 by cathepsin X. The latter is thus designated as a target for development of new antitumor strategies
    Source: PloS one [Elektronski vir]. - ISSN 1932-6203 (Vol. 8, iss. 1, 2013, str. 1-9, e53918)
    Type of material - e-article ; adult, serious
    Publish date - 2013
    Language - english
    COBISS.SI-ID - 3375217

    Link(s):

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053918
    DOI

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