دورية أكاديمية
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, Hausel, Jessica, Stierli, Salome, Treier, Mathias, Studer, Lorenz, Basler, Konrad, Levesque, Mitchell P., Dummer, Reinhard, Santoro, Raffaella, Cantù, Claudio, Sommer, Lukas |
| بيانات النشر: | Linköpings universitet, Avdelningen för molekylär medicin och virologi Linköpings universitet, Medicinska fakulteten Univ Zurich, Switzerland Univ Zurich, Switzerland; Mem Sloan Kettering Canc Ctr, NY 10021 USA Univ Hosp Zurich, Switzerland Max Delbruck Ctr Mol Med, Germany; Charite Univ Med Berlin, Germany Mem Sloan Kettering Canc Ctr, NY 10021 USA Nature Portfolio |
| سنة النشر: | 2021 |
| المجموعة: | Linköping University Electronic Press (LiU E-Press) |
| مصطلحات موضوعية: | Cell and Molecular Biology, Cell- och molekylärbiologi |
| 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::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. ; Funding Agencies|Functional Genomics Center Zurich (FGCZ) [p2155, p2419]; University of Zurich (University Priority Research Program (URPP) Translational Cancer Research); Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [31003A_169859, 310030_192075]; Swiss Cancer Research foundation [KFS-4570-08-2018]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; CancerfondenSwedish Cancer Society [CAN 2018/542]; Candoc Forschungskredit [FK-19-026] |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Nature Communications, 2021, 12:1; http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-178744Test; PMID 34417458; ISI:000687171500004 |
| DOI: | 10.1038/s41467-021-25326-8 |
| الإتاحة: | https://doi.org/10.1038/s41467-021-25326-8Test http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-178744Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9FC127FA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-021-25326-8 |
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