Cathepsin H mediates the processing of talin and regulates migration of prostate cancer cells.
J Biol Chem
; 288(4): 2201-9, 2013 Jan 25.
Article
in En
| MEDLINE
| ID: mdl-23204516
ABSTRACT
The cytoskeletal protein talin, an actin- and ß-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)ß(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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Talin
/
Cathepsin H
Limits:
Humans
/
Male
Language:
En
Journal:
J Biol Chem
Year:
2013
Document type:
Article
Affiliation country:
Slovenia