Evidence map›Paper›PMID 31013576›Full record

ArticleInternational journal of molecular sciences2019

Identification of ADAM12 as a Novel Basigin Sheddase.

Reidar Albrechtsen, Nicolai J Wewer Albrechtsen, Sebastian Gnosa, Jeanette Schwarz, Lars Dyrskjøt, Marie Kveiborg

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Article
  2. Article
  3. International journal of molecular sciences · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Soluble CD147 (BSG) as a Prognostic Marker in Multiple Myeloma.Current issues in molecular biology · 2022
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Matrix Metalloproteinases: How Much Can They Do?International journal of molecular sciences · 2020
    Article
  18. Article
  19. Review
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

6 authors.

Reidar AlbrechtsenBiotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. reidar.albrechtsen@bric.ku.dk.
Nicolai J Wewer AlbrechtsenDepartment of Biomedical Sciences and Department of Clinical Biochemistry, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. nicolai.albrechtsen@sund.ku.dk.ORCID 0000-0003-4230-5753
Sebastian GnosaBiotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. sebastian.gnosa@bric.ku.dk.
Jeanette SchwarzBiotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. j.schwarz@ikmb.uni-kiel.de.
Lars DyrskjøtDepartment of Molecular Medicine (MOMA), Aarhus University Hospital, 8200 Aarhus, Denmark. lars@clin.au.dk.ORCID 0000-0001-7061-9851
Marie KveiborgBiotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. marie.kveiborg@bric.ku.dk.ORCID 0000-0002-1293-1019

Funding

Danish Cancer Society R146-A9211-16-S2
6 · The paper itself

Abstract

The transmembrane glycoprotein basigin, a member of the immunoglobulin superfamily, stimulates matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) degradation and thereby drives cancer cell invasion. Basigin is proteolytically shed from the cell surface and high concentrations of soluble basigin in the blood dictates poor prognosis in cancer patients. A positive correlation between basigin and a disintegrin and metalloproteinase (ADAM)-12 in serum from prostate cancer patients has been reported. Yet, the functional relevance of this correlation is unknown. Here, we show that ADAM12 interacts with basigin and cleaves it in the juxtamembrane region. Specifically, overexpression of ADAM12 increases ectodomain shedding of an alkaline phosphatase-tagged basigin reporter protein from the cell surface. Moreover, CRISPR/Cas9-mediated knockout of ADAM12 in human HeLa carcinoma cells results in reduced shedding of the basigin reporter, which can be rescued by ADAM12 re-expression. We detected endogenous basigin fragments, corresponding to the expected size of the ADAM12-generated ectodomain, in conditioned media from ADAM12 expressing cancer cell-lines, as well as serum samples from a healthy pregnant donor and five bladder cancer patients, known to contain high ADAM12 levels. Supporting the cancer relevance of our findings, we identified several cancer-associated mutations in the basigin membrane proximal region. Subsequent in vitro expression showed that some of these mutants are more prone to ADAM12-mediated shedding and that the shed ectodomain can enhance gelatin degradation by cancer cells. In conclusion, we identified ADAM12 as a novel basigin sheddase with a potential implication in cancer.

Indexed as

ADAM12 ProteinAmino Acid SequenceBasiginCell LineCRISPR-Cas SystemsGene ExpressionGene Knockdown TechniquesGenes, ReporterHumansMutationSubstrate SpecificityADAM12 ProteinADAM12 protein, humanBasigina disintegrin and metalloproteinaseCD147ectodomain sheddingEMMPRIN

Identifiers

PMID31013576
PMCPMC6514901

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Registered trials

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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.