Evidence map›Paper›PMID 21211030›Full record

ArticleMolecular cancer2011

Efficient TGF-β/SMAD signaling in human melanoma cells associated with high c-SKI/SnoN expression.

Delphine Javelaud, Leon van Kempen, Vasileia I Alexaki, Erwan Le Scolan, Kunxin Luo, Alain Mauviel

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

22 citing papers in PubMed, 47 citations in OpenAlex.

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  11. Ski modulate the characteristics of pancreatic cancer stem cells via regulating sonic hedgehog signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
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  15. Other targeted drugs in melanoma.Annals of translational medicine · 2015
    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

6 authors at 4 institutions in 3 countries.

Delphine JavelaudInstitut Curie, University Center, Building 110, Orsay, France.
Leon van Kempen
Vasileia I Alexaki
Erwan Le Scolan
Kunxin Luo
Alain Mauviel
Institut Curie · FRUniversity of California, Berkeley · USCentre National de la Recherche Scientifique · FRRadboud University Nijmegen · NL

Funding

Ski proto-oncogene in development and oncognesisR01CA101891 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI LUO, KUNXIN · 2004 to 2009
$1.2M
NCI NIH HHS R01 CA101891
6 · The paper itself

Abstract

backgroundSKI and SnoN proteins have been shown to inhibit TGF-β signaling, acting both as transcriptional co-repressors in the cell nucleus, and as sequestrators of SMAD proteins in the cytoplasm. TGF-β, on the other hand, induces rapid, proteasome-mediated, degradation of both proteins. How elevated SKI and SnoN protein levels co-exist with active autocrine TGF-β signaling in cancer cells is yet to be understood.

resultsIn this study, we found elevated SKI and SnoN protein levels in a panel of melanoma cell lines, as compared to normal melanocytes. There was no correlation between SKI protein content and the capacity of melanoma cells to invade Matrigel™, to form subcutaneous tumors, or to metastasize to bone after intracardiac inoculation into nude mice. Nor did we find a correlation between SKI expression and histopathological staging of human melanoma. TGF-β induced a rapid and dose-dependent degradation of SKI protein, associated with SMAD3/4 specific transcriptional response and induction of pro-metastatic target genes, partially prevented by pharmacologic blockade of proteasome activity. SKI knockdown in 1205Lu melanoma cells did not alter their invasive capacity or transcriptional responses to TGF-β, and did not allow p21 expression in response to TGF-β or reveal any growth inhibitory activity of TGF-β.

conclusionsDespite high expression in melanoma cells, the role of SKI in melanoma remains elusive: SKI does not efficiently interfere with the pro-oncogenic activities of TGF-β, unless stabilized by proteasome blockade. Its highly labile nature makes it an unlikely target for therapeutic intervention.

Indexed as

AnimalsCell LineCell Line, TumorCell ProliferationCyclin-Dependent Kinase Inhibitor p21DNA-Binding ProteinsGene Knockdown TechniquesHumansIntracellular Signaling Peptides and ProteinsLeupeptinsMelanomaMiceMice, NudeNeoplasm InvasivenessNeoplasm MetastasisNeoplasm Transplantationbenzyloxycarbonylleucyl-leucyl-leucine aldehydeCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21DNA-Binding ProteinsIntracellular Signaling Peptides and ProteinsLeupeptinsProteasome InhibitorsProto-Oncogene ProteinsSKIL protein, humanSKI protein, humanSmad ProteinsTransforming Growth Factor beta

Identifiers

PMID21211030
PMCPMC3025974
OpenAlexW2105562887

What OpenQuestion holds

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LicenceCC BY
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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.