SATB1 in Malignant T Cells

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Simon Fredholm
  • Andreas Willerslev-Olsen
  • Özcan Met
  • Linda Kubat
  • Maria Gluud
  • Sarah L. Mathiasen
  • Christina Friese
  • Edda Blümel
  • David L. Petersen
  • Tengpeng Hu
  • Claudia Nastasi
  • Lise M. Lindahl
  • Terkild B. Buus
  • Thorbjørn Krejsgaard
  • Mariusz A. Wasik
  • Katharina L. Kopp
  • Sergei B. Koralov
  • Jenny L. Persson
  • Charlotte M. Bonefeld
  • Carsten Geisler
  • And 4 others
  • Anders Woetmann
  • Lars Iversen
  • Jürgen C. Becker
  • Niels Ødum
Organisations
External organisations
  • University of Copenhagen
  • University of Pennsylvania
  • New York University
  • Umeå University
  • German Cancer Research Centre
  • Aarhus University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)1805-1815
JournalJournal of Investigative Dermatology
Volume138
Issue number8
Early online date2018 Jan 1
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes