title: Cathepsin H mediates the processing of talin and regulates migration of prostate cancer cells.
abstract: The cytoskeletal protein talin, an actin- and β-integrin tail-binding protein, plays an important role in cell migration by promoting integrin activation and focal adhesion formation. Here, we show that talin is a substrate for cathepsin H (CtsH), a lysosomal cysteine protease with a strong aminopeptidase activity. Purified active CtsH sequentially cleaved a synthetic peptide representing the N terminus of the talin F0 head domain. The processing of talin by CtsH was determined also in the metastatic PC-3 prostate cancer cell line, which exhibits increased expression of CtsH. The attenuation of CtsH aminopeptidase activity by a specific inhibitor or siRNA-mediated silencing significantly reduced the migration of PC-3 cells on fibronectin and invasion through Matrigel. We found that in migrating PC-3 cells, CtsH was co-localized with talin in the focal adhesions. Furthermore, specific inhibition of CtsH increased the activation of α(v)β(3)-integrin on PC-3 cells. We propose that CtsH-mediated processing of talin might promote cancer cell progression by affecting integrin activation and adhesion strength.
authors.affiliation: Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia. zala.jevnikar@ffa.uni-lj.si
authors.forename: Zala
authors.initials: Z
authors.lastname: Jevnikar
authors.forename: Matija
authors.initials: M
authors.lastname: Rojnik
authors.forename: Polona
authors.initials: P
authors.lastname: Jamnik
authors.forename: Bojan
authors.initials: B
authors.lastname: Doljak
authors.forename: Urša Pečar
authors.initials: UP
authors.lastname: Fonovic
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry; D056655:Cathepsin H / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D016608:Talin / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D016023:Integrins; D034741:RNA, Small Interfering; D016608:Talin; D000626:Aminopeptidases; D056655:Cathepsin H