Imperial College London
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DrElenaDe Vita

Faculty of Natural Sciences, Department of Chemistry

 
 
 
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e.de-vita17 CV

 
 
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Location

 

Molecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lovell:2021:10.1101/2021.04.15.439906,
author = {Lovell, S and Zhang, L and Kryza, T and Neodo, A and Bock, N and Williams, ED and Engelsberger, E and Xu, C and Bakker, AT and De, Vita E and Maneiro, M and Tanaka, RJ and Bevan, CL and Clements, JA and Tate, EW},
doi = {10.1101/2021.04.15.439906},
title = {A suite of activity-based probes to dissect the KLK activome in drug-resistant prostate cancer},
url = {http://dx.doi.org/10.1101/2021.04.15.439906},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>Kallikrein-related peptidases (KLKs) are a family of secreted serine proteases, which form a network – the KLK activome – with an important role in proteolysis and signaling. In prostate cancer (PCa), increased KLK activity promotes tumor growth and metastasis through multiple biochemical pathways, and specific quantification and tracking of changes in the KLK activome could contribute to validation of KLKs as potential drug targets. Herein we report a technology platform based on novel activity-based probes (ABPs) and inhibitors with unprecedented potency and selectivity enabling simultaneous orthogonal analysis of KLK2, KLK3 and KLK14 activity in hormone-responsive PCa cell lines and tumor homogenates. Using selective inhibitors and multiplexed fluorescent activity-based protein profiling (ABPP) we dissect the KLK activome in PCa cells and show that increased KLK14 activity leads to a migratory phenotype. Furthermore, using biotinylated ABPs we show that active KLK molecules are secreted into the bone microenvironment by PCa cells following stimulation by osteoblasts suggesting KLK-mediated signaling mechanisms could contribute to PCa metastasis to bone. Together our findings show that ABPP is a powerful approach to dissect dysregulation of the KLK activome as a promising and previously underappreciated therapeutic target in advanced PCa.</jats:p>
AU  - Lovell,S
AU  - Zhang,L
AU  - Kryza,T
AU  - Neodo,A
AU  - Bock,N
AU  - Williams,ED
AU  - Engelsberger,E
AU  - Xu,C
AU  - Bakker,AT
AU  - De,Vita E
AU  - Maneiro,M
AU  - Tanaka,RJ
AU  - Bevan,CL
AU  - Clements,JA
AU  - Tate,EW
DO  - 10.1101/2021.04.15.439906
PY  - 2021///
TI  - A suite of activity-based probes to dissect the KLK activome in drug-resistant prostate cancer
UR  - http://dx.doi.org/10.1101/2021.04.15.439906
ER  -
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