Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/29261
Title: High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response.
Authors: 
Issue Date: 14-Dec-2017
Citation: Oncogenesis.2017 Dec;(6)12:401
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.
PMID: 29284798
URI: https://hdl.handle.net/20.500.12530/29261
Rights: openAccess
ISSN: 2157-9024
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. La Paz > Artículos
Hospitales > H. U. La Paz > Artículos

Files in This Item:
File Description SizeFormat 
PMC5865544.pdf1.46 MBAdobe PDFThumbnail
View/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.