Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4
| العنوان: | Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4 |
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| المؤلفون: | Diener, Johanna, Baggiolini, Arianna, Pernebrink, Mattias, Dalcher, Damian, Lerra, Luigi, Cheng, Phil F, Varum, Sandra, Häusel, Jessica, Stierli, Salome, Treier, Mathias, Studer, Lorenz, Basler, Konrad, Levesque, Mitchell P, Dummer, Reinhard, Santoro, Raffaella, Cantù, Claudio, Sommer, Lukas |
| المساهمون: | University of Zurich, Sommer, Lukas |
| المصدر: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021) |
| بيانات النشر: | Nature Publishing Group UK, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Skin Neoplasms, 10017 Institute of Anatomy, Carcinogenesis, Science, Cell- och molekylärbiologi, General Physics and Astronomy, Histone Deacetylase 2, Mice, Nude, 1600 General Chemistry, Genetics and Molecular Biology, Mice, Transgenic, Article, Metastasis, Epigenesis, Genetic, Histones, 1300 General Biochemistry, Genetics and Molecular Biology, Cell Line, Tumor, Cell Adhesion, Animals, Humans, Cell Lineage, Neoplasm Invasiveness, Melanoma, Cell Proliferation, Stem Cell Factor, Base Sequence, Gene Expression Profiling, fungi, 10177 Dermatology Clinic, Acetylation, General Chemistry, 10226 Department of Molecular Mechanisms of Disease, 10124 Institute of Molecular Life Sciences, 3100 General Physics and Astronomy, eye diseases, Tumor Burden, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Cardiovascular and Metabolic Diseases, Neoplasm Micrometastasis, General Biochemistry, 570 Life sciences, biology, Melanocytes, Cell and Molecular Biology, Protein Binding, Transcription Factors |
| الوصف: | 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::NrasQ61K; 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. |
| وصف الملف: | application/pdf; s41467-021-25326-8.pdf - application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0a1806e7394f6ca6b315413bb0108bbTest http://europepmc.org/articles/PMC8379183Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b0a1806e7394f6ca6b315413bb0108bb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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