Journal of Biological Chemistry
Volume 288, Issue 4, 25 January 2013, Pages 2201-2209
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Cell Biology
Cathepsin H Mediates the Processing of Talin and Regulates Migration of Prostate Cancer Cells*

https://doi.org/10.1074/jbc.M112.436394Get rights and content
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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 αvβ3-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.

Background: Cathepsin H (CtsH) is an aminopeptidase that is involved in tumor progression.

Results: CtsH cleaves talin, and its inhibition reduces the migration of prostate cancer cells.

Conclusion: CtsH affects cell migration by influencing the activity of integrins, a process that could be regulated by talin cleavage.

Significance: Identification of novel CtsH proteolytic targets is important to understand and control tumor progression.

Cell Migration
Cysteine Protease
Integrins
Molecular Cell Biology
Tumor Cell Biology

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*

This work was supported by Slovenian Research Agency Grants P4 0127 and J4 4123 (to J. K.).

This article contains supplemental Figs. S1–S3.

1

Both authors contributed equally to this work.