Cathepsin H mediates the processing of talin and regulates migration of prostate cancer cells
Jevnikar, Zala (Author), Rojnik, Matija (Author), Jamnik, Polona (Author), Doljak, Bojan (Author), Pečar Fonović, Urša (Author), Kos, Janko (Author)

URLURL - Presentation file, Visit http://www.jbc.org/content/288/4/2201.abstract This link opens in a new window

The cytoskeletal protein talin, an actin- and Ž-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 Ž(v)Ž(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.

Keywords:katepsin H, cisteinske proteaze, CtsH, rak prostate
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 2201-2209
Numbering:Vol. 288
ISSN on article:0021-9258
DOI:10.1074/jbc.M112.436394 Link is opened in a new window
COBISS.SI-ID:3390321 Link is opened in a new window
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Record is a part of a journal

Title:#The #Journal of biological chemistry
Shortened title:J Biol Chem
Publisher:American Society of Biological Chemists.
COBISS.SI-ID:6326023 This link opens in a new window

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