Evidence map›Paper›PMID 22988297›Full record

ArticleMolecular and cellular biology2012

A phosphatidylinositol 3-kinase-Pax3 axis regulates Brn-2 expression in melanoma.

Elise Bonvin, Paola Falletta, Heather Shaw, Veronique Delmas, Colin R Goding

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 47 citations in OpenAlex.

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  14. MITF-the first 25 years.Genes & development · 2019
    Review
  15. Article
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  17. The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology.Laboratory investigation; a journal of technical methods and pathology · 2017
    Review
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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

5 authors at 2 institutions in 2 countries.

Elise BonvinLudwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Headington, Oxford, United Kingdom.
Paola Falletta
Heather Shaw
Veronique Delmas
Colin R Goding
University of Oxford · GBCentre National de la Recherche Scientifique · FR

Funding

Wellcome Trust
6 · The paper itself

Abstract

Deregulation of transcription arising from mutations in key signaling pathways is a hallmark of cancer. In melanoma, the most aggressive and lethal form of skin cancer, the Brn-2 transcription factor (POU3F2) regulates proliferation and invasiveness and lies downstream from mitogen-activated protein kinase (MAPK) and Wnt/β-catenin, two melanoma-associated signaling pathways. In vivo Brn-2 represses expression of the microphthalmia-associated transcription factor, MITF, to drive cells to a more stem cell-like and invasive phenotype. Given the key role of Brn-2 in regulating melanoma biology, understanding the signaling pathways that drive Brn-2 expression is an important issue. Here, we show that inhibition of phosphatidylinositol 3-kinase (PI3K) signaling reduces invasiveness of melanoma cells in culture and strongly inhibits Brn-2 expression. Pax3, a transcription factor regulating melanocyte lineage-specific genes, directly binds and regulates the Brn-2 promoter, and Pax3 expression is also decreased upon PI3K inhibition. Collectively, our results highlight a crucial role for PI3K in regulating Brn-2 and Pax3 expression, reveal a mechanism by which PI3K can regulate invasiveness, and imply that PI3K signaling is a key determinant of melanoma subpopulation diversity. Together with our previous work, the results presented here now place Brn-2 downstream of three melanoma-associated signaling pathways.

Indexed as

Gene Expression Regulation, NeoplasticPhosphoinositide-3 Kinase InhibitorsAnimalsCell Line, TumorCell ProliferationHomeodomain ProteinsHumansMelanomaMiceMitogen-Activated Protein Kinase KinasesNeoplasm InvasivenessPaired Box Transcription FactorsPAX3 Transcription FactorPhosphatidylinositol 3-KinasesPOU Domain FactorsPromoter Regions, GeneticHomeodomain ProteinsMitogen-Activated Protein Kinase KinasesPaired Box Transcription FactorsPAX3 protein, humanPAX3 Transcription FactorPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPOU Domain Factorstranscription factor Brn-2Wnt Proteins

Identifiers

PMID22988297
PMCPMC3486186
OpenAlexW2131790747

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.