ArticleJournal of the American Chemical Society2021
A Suite of Activity-Based Probes To Dissect the KLK Activome in Drug-Resistant Prostate Cancer.
Article in Journal of the American Chemical Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Beyond the catalytic serine: selective protease engagement with covalent macrocyclic activity-based probes.Chemical science · 2026Article
- Scaling covalent ligand discovery through dynamic combinatorial library-versus-proteome screening.Nature communications · 2026Article
- Kallikrein related peptidases 7 and 10 and their substrate desmoglein 3 are upregulated in early stage pancreatic cancerous lesions.Scientific reports · 2026Article
- Enhanced nodal staging by molecular detection of KLK3, FOLH1, and PCA3 in prostate cancer.Discover oncology · 2026Article
- Utilizing Two Electrokinetic Techniques on a Single Device for Detection of Extracellular Vesicle-Associated Protease Activity.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Epidermal growth factor receptor contributes to indirect regulation of skeletal muscle mass by androgen.Endocrine journal · 2025Article
- Chemical biology tools for protein labelling: insights into cell-cell communication.The Biochemical journal · 2023Review
- Chemical Tools to Image the Activity of PAR-Cleaving Proteases.ACS bio & med chem Au · 2023Review
- The roles of proteases in prostate cancer.IUBMB life · 2023Review
- Novel specific activity-based probes validate KLK proteases as druggable targets.Cancer biology & therapy · 2022Article
- Drugging the undruggable: activity-based protein profiling offers opportunities for targeting the KLK activome.Cancer biology & therapy · 2022Article
- A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell Invasion.Journal of the American Chemical Society · 2022Article
- Co-Crystal Structure-Guided Optimization of Dual-Functional Small Molecules for Improving the Peroxygenase Activity of Cytochrome P450BM3.International journal of molecular sciences · 2022Article
- Activity-Based Probes for Proteases Pave the Way to Theranostic Applications.Pharmaceutics · 2022Review
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- Novel inhibitors and activity-based probes targeting serine proteases.Frontiers in chemistry · 2022Article
- Novel Inhibitors and Activity-Based Probes Targeting Trypsin-Like Serine Proteases.Frontiers in chemistry · 2022Article
- Role of Serine Proteases at the Tumor-Stroma Interface.Frontiers in immunology · 2022Review
- KLK3 in the Regulation of Angiogenesis-Tumorigenic or Not?International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
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 enabling simultaneous orthogonal analysis of KLK2, KLK3, and KLK14 activity in hormone-responsive PCa cell lines and tumor homogenates. Importantly, we identifed a significant decoupling of KLK activity and abundance and suggest that KLK proteolysis should be considered as an additional parameter, along with the PSA blood test, for accurate PCa diagnosis and monitoring. 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.