Edinburgh Research Explorer

High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response

Research output: Contribution to journalArticle

  • Olatz Arrizabalaga
  • Leire Moreno-Cugnon
  • Jaione Auzmendi-Iriarte
  • Paula Aldaz
  • Inmaculada Ibañez de Cáceres
  • Laura Garros-Regulez
  • Veronica Moncho-Amor
  • Sergio Torres-Bayona
  • Olga Pernía
  • Laura Pintado-Berninches
  • Patricia Carrasco-Ramirez
  • María Cortes-Sempere
  • Rocío Rosas
  • Pilar Sanchez-Gomez
  • Irune Ruiz
  • Helena Caren
  • Idoia Garcia
  • Angel-Ayuso Sacido
  • Robin Lovell-Badge
  • Cristobal Belda-Iniesta
  • Nicolas Sampron
  • Rosario Perona
  • Ander Matheu

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

    Final published version, 1.38 MB, PDF document

    Licence: Creative Commons: Attribution (CC-BY)

Original languageEnglish
Pages (from-to)401
JournalOncogenesis
Volume6
Issue number12
Early online date14 Dec 2017
DOIs
Publication statusE-pub ahead of print - 14 Dec 2017

Abstract

The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC. Notably, we find that high levels of MKP1 correlate with a subset of glioblastoma patients with better prognosis and overall increased survival. Gain of expression studies demonstrated that elevated MKP1 impairs self-renewal and induces differentiation of GSCs while reducing tumorigenesis in vivo. Moreover, we identified that MKP1 is epigenetically regulated and that it mediates the anti-tumor activity of histone deacetylase inhibitors (HDACIs) alone or in combination with temozolomide. In summary, this study identifies MKP1 as a key modulator of the interplay between GSC self-renewal and differentiation and provides evidence that the activation of MKP1, through epigenetic regulation, might be a novel therapeutic strategy to overcome therapy resistance in glioblastoma.

    Research areas

  • Journal Article

Download statistics

No data available

ID: 51283911