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Epigenetic control ...
Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4
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- Diener, Johanna (author)
- Univ Zurich, Switzerland
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- Baggiolini, Arianna (author)
- Univ Zurich, Switzerland; Mem Sloan Kettering Canc Ctr, NY 10021 USA
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- Pernebrink, Mattias (author)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
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- Dalcher, Damian (author)
- Univ Zurich, Switzerland
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- Lerra, Luigi (author)
- Univ Zurich, Switzerland
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- Cheng, Phil F. (author)
- Univ Hosp Zurich, Switzerland
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- Varum, Sandra (author)
- Univ Zurich, Switzerland
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- Hausel, Jessica (author)
- Univ Zurich, Switzerland
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- Stierli, Salome (author)
- Univ Zurich, Switzerland
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- Treier, Mathias (author)
- Max Delbruck Ctr Mol Med, Germany; Charite Univ Med Berlin, Germany
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- Studer, Lorenz (author)
- Mem Sloan Kettering Canc Ctr, NY 10021 USA
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- Basler, Konrad (author)
- Univ Zurich, Switzerland
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- Levesque, Mitchell P. (author)
- Univ Hosp Zurich, Switzerland
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- Dummer, Reinhard (author)
- Univ Hosp Zurich, Switzerland
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- Santoro, Raffaella (author)
- Univ Zurich, Switzerland
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- Cantù, Claudio, 1981- (author)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Univ Zurich, Switzerland,Wallenberg Centre for Molecular Medicine
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- Sommer, Lukas (author)
- Univ Zurich, Switzerland
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(creator_code:org_t)
- 2021-08-20
- 2021
- English.
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In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 12:1
- Related links:
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https://liu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::Nras(Q61K); Cdkn2a(-/-) melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism. Melanoma cells can switch between proliferative and invasive phenotypes. Here the authors show that the embryonic stem cell factor Sall4 is a negative regulator of melanoma phenotype switching where its loss leads to the acquisition of an invasive phenotype, due to derepression of invasiveness genes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Diener, Johanna
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Baggiolini, Aria ...
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Pernebrink, Matt ...
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Dalcher, Damian
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Lerra, Luigi
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Cheng, Phil F.
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Varum, Sandra
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Hausel, Jessica
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Stierli, Salome
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Treier, Mathias
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Studer, Lorenz
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Basler, Konrad
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Levesque, Mitche ...
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Dummer, Reinhard
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Santoro, Raffael ...
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Cantù, Claudio, ...
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Sommer, Lukas
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature Communica ...
- By the university
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Linköping University