Evidence map›Paper›PMID 24120346›Full record

ArticleMolecular oncology2014

Secretome and degradome profiling shows that Kallikrein-related peptidases 4, 5, 6, and 7 induce TGFβ-1 signaling in ovarian cancer cells.

Hasmik Shahinian, Daniela Loessner, Martin L Biniossek, Jayachandran N Kizhakkedathu, Judith A Clements, Viktor Magdolen, Oliver Schilling

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
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  3. The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine.International journal of molecular sciences · 2022
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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

7 authors at 4 institutions in 3 countries.

Hasmik ShahinianInstitute of Molecular Medicine and Cell Research, University of Freiburg, D-79104 Freiburg, Germany.
Daniela LoessnerCancer Program, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland 4059, Australia.
Martin L BiniossekInstitute of Molecular Medicine and Cell Research, University of Freiburg, D-79104 Freiburg, Germany.
Jayachandran N KizhakkedathuCentre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Judith A ClementsCancer Program, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland 4059, Australia.
Viktor MagdolenClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, D-81675, Germany.
Oliver SchillingInstitute of Molecular Medicine and Cell Research, University of Freiburg, D-79104 Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, University of Freiburg, D-79104 Freiburg, Germany. Electronic address: oliver.schilling@mol-med.uni-freiburg.de.
University of Freiburg · DEQueensland University of Technology · AUTechnical University of Munich · DEUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kallikrein-related peptidases, in particular KLK4, 5, 6 and 7 (4-7), often have elevated expression levels in ovarian cancer. In OV-MZ-6 ovarian cancer cells, combined expression of KLK4-7 reduces cell adhesion and increases cell invasion and resistance to paclitaxel. The present work investigates how KLK4-7 shape the secreted proteome ("secretome") and proteolytic profile ("degradome") of ovarian cancer cells. The secretome comparison consistently identified >900 proteins in three replicate analyses. Expression of KLK4-7 predominantly affected the abundance of proteins involved in cell-cell communication. Among others, this includes increased levels of transforming growth factor β-1 (TGFβ-1). KLK4-7 co-transfected OV-MZ-6 cells share prominent features of elevated TGFβ-1 signaling, including increased abundance of neural cell adhesion molecule L1 (L1CAM). Augmented levels of TGFβ-1 and L1CAM upon expression of KLK4-7 were corroborated in vivo by an ovarian cancer xenograft model. The degradomic analysis showed that KLK4-7 expression mostly affected cleavage sites C-terminal to arginine, corresponding to the preference of kallikreins 4, 5 and 6. Putative kallikrein substrates include chemokines, such as growth differentiation factor 15 (GDF 15) and macrophage migration inhibitory factor (MIF). Proteolytic maturation of TGFβ-1 was also elevated. KLK4-7 have a pronounced, yet non-degrading impact on the secreted proteome, with a strong association between these proteases and TGFβ-1 signaling in tumor biology.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsCell Line, TumorFemaleHumansKallikreinsMiceOvarian NeoplasmsOvaryProteolysisSignal TransductionTransforming Growth Factor beta1Up-RegulationKallikreinsTransforming Growth Factor beta1DegradomicsKallikrein-related proteasesOvarian cancerProteolysisTransforming growth factor beta

Identifiers

PMID24120346
PMCPMC5528505
OpenAlexW2082444360

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.