Evidence map›Paper›PMID 19177143›Full record

ArticleThe Journal of investigative dermatology2009

Wnt5A activates the calpain-mediated cleavage of filamin A.

Michael P O'Connell, Jennifer L Fiori, Katherine M Baugher, Fred E Indig, Amanda D French, Tura C Camilli, Brittany P Frank, Rachel Earley, Keith S Hoek, Joanne H Hasskamp and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of investigative dermatology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

39 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
  2. Role of the Ror family receptors in Wnt5a signaling.In vitro cellular & developmental biology. Animal · 2024
    Review
  3. The Role of Calcium Signaling in Melanoma.International journal of molecular sciences · 2022
    Review
  4. Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2021
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Wnt signaling in cancer.Oncogene · 2017
    Review
  10. Article
  11. Article
  12. Review
  13. WNT-5A: signaling and functions in health and disease.Cellular and molecular life sciences : CMLS · 2016
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response.Proceedings of the National Academy of Sciences of the United States of America · 2014
    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 at 3 institutions in 2 countries.

Michael P O'ConnellLaboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Jennifer L Fiori
Katherine M Baugher
Fred E Indig
Amanda D French
Tura C Camilli
Brittany P Frank
Rachel Earley
Keith S Hoek
Joanne H Hasskamp
E George Elias
Dennis D Taub
Michel Bernier
Ashani T Weeraratna
National Institutes of Health · USHarry and Jeanette Weinberg Foundation · USUniversity Hospital of Zurich · CH

Funding

NIA/RRB Confocal Imaging FacilityZICAG000615 · NIA · NATIONAL INSTITUTE ON AGING · PI INDIG, FRED · 2009 to 2025
$17.9M
Using gene expression profiles to elucidate mechanisms of melanoma progressionZ01AG000442 · NIA · NATIONAL INSTITUTE ON AGING · PI WEERARATNA, ASHANI · 2004 to 2008
$1.3M
Role of Filamin A in Inflammation and OncogenesisZIAAG000892 · NIA · NATIONAL INSTITUTE ON AGING · PI BERNIER, MICHEL · 2009 to 2011
$1.0M
Role of Wnt Signaling in melanoma metastasis and melanocyte differentiationZIAAG000450 · NIA · NATIONAL INSTITUTE ON AGING · PI WEERARATNA, ASHANI · 2009 to 2010
$462k
Using gene expression profiles to elucidate mechanisms of melanoma progressionZIAAG000442 · NIA · NATIONAL INSTITUTE ON AGING · PI WEERARATNA, ASHANI · 2009 to 2010
$443k
Intramural NIH HHS Z01 AG000442
6 · The paper itself

Abstract

We have previously shown that Wnt5A and ROR2, an orphan tyrosine kinase receptor, interact to mediate melanoma cell motility. In other cell types, this can occur through the interaction of ROR2 with the cytoskeletal protein filamin A. Here, we found that filamin A protein levels correlated with Wnt5A levels in melanoma cells. Small interfering RNA (siRNA) knockdown of WNT5A decreased filamin A expression. Knockdown of filamin A also corresponded to a decrease in melanoma cell motility. In metastatic cells, filamin A expression was predominant in the cytoplasm, which western analysis indicated was due to the cleavage of filamin A in these cells. Treatment of nonmetastatic melanoma cells with recombinant Wnt5A increased filamin A cleavage, and this could be prevented by the knockdown of ROR2 expression. Further, BAPTA-AM chelation of intracellular calcium also inhibited filamin A cleavage, leading to the hypothesis that Wnt5A/ROR2 signaling could cleave filamin A through activation of calcium-activated proteases, such as calpains. Indeed, WNT5A knockdown decreased calpain 1 expression, and by inhibiting calpain 1 either pharmacologically or using siRNA, it decreased cell motility. Our results indicate that Wnt5A activates calpain-1, leading to the cleavage of filamin A, which results in a remodeling of the cytoskeleton and an increase in melanoma cell motility.

Indexed as

CalpainCell Line, TumorCell MovementChelating AgentsContractile ProteinsCytoskeletonEgtazic AcidFilaminsGene Expression Regulation, NeoplasticHumansMelanomaMicrofilament ProteinsProto-Oncogene ProteinsReceptors, Cell SurfaceReceptor Tyrosine Kinase-like Orphan ReceptorsRNA, Small Interfering1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl esterCalpainCAPN1 protein, humanChelating AgentsContractile ProteinsEgtazic AcidFilaminsMicrofilament ProteinsProto-Oncogene ProteinsReceptors, Cell SurfaceReceptor Tyrosine Kinase-like Orphan ReceptorsRNA, Small InterferingROR2 protein, humanWnt-5a ProteinWNT5A protein, humanWnt Proteins

Identifiers

PMID19177143
PMCPMC2695838
OpenAlexW1978871305

What OpenQuestion holds

Textmetadata
LicenceTDM
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.