SATB1 in Malignant T Cells.
| Autor: | Fredholm S; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Willerslev-Olsen A; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Met Ö; Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Kubat L; Translational Skin Cancer Research, German Cancer Consortium (DKTK and DKFZ), Partner Site Essen, Essen, Germany., Gluud M; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Mathiasen SL; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Friese C; Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Blümel E; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Petersen DL; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Hu T; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Nastasi C; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Lindahl LM; Department of Dermatology, Aarhus University Hospital, Skejby, Aarhus, Denmark., Buus TB; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Krejsgaard T; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Wasik MA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Kopp KL; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Koralov SB; Department of Pathology, New York University School of Medicine, New York, New York, USA., Persson JL; Division of Experimental Cancer Research, Department of Translational Medicine, Lund University, Clinical Research Centre, Malmö, Sweden; Division of Basal Tumor Biology, Department of Molecular Biology, Umeå University, Umeå, Sweden., Bonefeld CM; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Geisler C; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Woetmann A; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Iversen L; Department of Dermatology, Aarhus University Hospital, Skejby, Aarhus, Denmark., Becker JC; Translational Skin Cancer Research, German Cancer Consortium (DKTK and DKFZ), Partner Site Essen, Essen, Germany. Electronic address: j.becker@dkfz-heidelberg.de., Ødum N; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. Electronic address: ndum@sund.ku.dk. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of investigative dermatology [J Invest Dermatol] 2018 Aug; Vol. 138 (8), pp. 1805-1815. Date of Electronic Publication: 2018 May 08. |
| DOI: | 10.1016/j.jid.2018.03.1526 |
| Abstrakt: | Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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