Evidence map›Paper›PMID 39937919›Full record

ArticleScience advances2025

Targeted approach to determine the impact of cancer-associated protease variants.

Kira Bickenbach, Nele David, Tomas Koudelka, Corentin Joos, Franka Scharfenberg, Malina Rüffer, Fred Armbrust, Dimitris Georgiadis, Fabrice Beau, Lea Stahmer and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Meprin β is specifically inhibited by its cognate synthetic propeptide.Cellular and molecular life sciences : CMLS · 2026
    Article
  3. Review
  4. Article
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

14 authors.

Kira BickenbachUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.ORCID 0000-0001-5079-0512
Nele DavidUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.ORCID 0009-0009-3589-8264
Tomas KoudelkaSystematic Proteomics and Bioanalytics, Institute for Experimental Medicine, University of Kiel, Kiel, Germany.
Corentin JoosUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.ORCID 0009-0003-1270-0223
Franka ScharfenbergUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.
Malina RüfferUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.
Fred ArmbrustUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.ORCID 0000-0002-3331-5522
Dimitris GeorgiadisLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0002-9656-0701
Fabrice BeauCEA, INRAE, Medicaments et Technologies pour la Sante (MTS), SIMoS, Université Paris-Saclay, Gif-sur-Yvette, France.
Lea StahmerUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.ORCID 0009-0005-5307-3638
Sascha RahnUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.
Andreas TholeySystematic Proteomics and Bioanalytics, Institute for Experimental Medicine, University of Kiel, Kiel, Germany.ORCID 0000-0002-8687-6817
Claus PietrzikInstitute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.ORCID 0000-0002-1202-5489
Christoph Becker-PaulyUnit for Degradomics of the Protease Web, Biochemical Institute, University of Kiel, Kiel, Germany.ORCID 0000-0002-5100-9916

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several steps of cancer progression, from tumor onset to metastasis, critically involve proteolytic activity. To elucidate the role of proteases in cancer, it is particularly important to consider single-nucleotide variants (SNVs) that affect the active site of proteases, thereby influencing cleavage specificity, substrate processing, and thus cancer cell behavior. To facilitate systematic studies, we here present a targeted approach to determine the impact of cancer-associated protease variants (TACAP). Starting with the semiautomated identification of potential specificity-modulating SNVs, our workflow comprises mass spectrometry-based cleavage specificity profiling and substrate identification, localization, and inhibitor studies, followed by functional analyses investigating cancer cell properties. To demonstrate the feasibility of TACAP, we analyzed the meprin β R238Q variant. This amino acid exchange R238Q leads to a loss of meprin β's characteristic cleavage preference for acidic amino acids at P1' position, accompanied with changes in substrate pool and inhibitor affinity compared to meprin β wild type.

Indexed as

MetalloendopeptidasesNeoplasmsPeptide HydrolasesPolymorphism, Single NucleotideCell Line, TumorHumansProteolysisSubstrate SpecificityMetalloendopeptidasesPeptide Hydrolases

Identifiers

PMID39937919
PMCPMC11818018

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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.