Evidence map›Paper›PMID 33859413›Full record

ArticleNature chemical biology2021

Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1.

Thomas Kryza, Tashbib Khan, Scott Lovell, Brittney S Harrington, Julia Yin, Sean Porazinski, Marina Pajic, Hannu Koistinen, Juha K Rantala, Tobias Dreyer and 5 more

Abstract read
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In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 5 countries.

Thomas Kryza *Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.ORCID http://orcid.org/0000-0003-1668-8551
Tashbib Khan *Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.ORCID http://orcid.org/0000-0001-5203-0672
Scott Lovell *Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, London, UK.
Brittney S HarringtonMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.ORCID http://orcid.org/0000-0001-7083-069X
Julia YinThe Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-7706-5895
Sean PorazinskiThe Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Marina PajicThe Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Hannu KoistinenDepartment of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.ORCID http://orcid.org/0000-0003-0926-3109
Juha K RantalaMisvik Biology, Turku, Finland.ORCID http://orcid.org/0000-0002-4999-5585
Tobias DreyerClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.
Viktor MagdolenClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.
Ute ReuningClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.
Yaowu HeMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.ORCID http://orcid.org/0000-0002-7828-263X
Edward W TateDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, London, UK.ORCID http://orcid.org/0000-0003-2213-5814
John D HooperMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia. john.hooper@mater.uq.edu.au.ORCID http://orcid.org/0000-0003-1054-8486
Translational Research Institute · AUGarvan Institute of Medical Research · AUTechnical University of Munich · DEImperial College London · GBTurku Centre for Biotechnology · FIUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CUB domain-containing protein 1 (CDCP1) is an oncogenic orphan transmembrane receptor and a promising target for the detection and treatment of cancer. Extracellular proteolysis of CDCP1 by poorly defined mechanisms induces pro-metastatic signaling. We describe a new approach for the rapid identification of proteases responsible for key proteolytic events using a substrate-biased activity-based probe (sbABP) that incorporates a substrate cleavage motif grafted onto a peptidyl diphenyl phosphonate warhead for specific target protease capture, isolation and identification. Using a CDCP1-biased probe, we identify urokinase (uPA) as the master regulator of CDCP1 proteolysis, which acts both by directly cleaving CDCP1 and by activating CDCP1-cleaving plasmin. We show that coexpression of uPA and CDCP1 is strongly predictive of poor disease outcome across multiple cancers and demonstrate that uPA-mediated CDCP1 proteolysis promotes metastasis in disease-relevant preclinical in vivo models. These results highlight CDCP1 cleavage as a potential target to disrupt cancer and establish sbABP technology as a new approach to identify disease-relevant proteases.

Indexed as

AnimalsAntigens, NeoplasmCell Adhesion MoleculesHumansMiceMice, Inbred NODMice, SCIDMolecular StructurePeptide HydrolasesSubstrate SpecificityAntigens, NeoplasmCDCP1 protein, humanCell Adhesion MoleculesPeptide Hydrolases

Identifiers

PMID33859413
OpenAlexW3155580966

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.