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High levels of MKP1 correlate with a higher sensitivity to chemotherapy in Glioblastoma patients associated to a differentiation of the cancer stem cells

O. Arrizabalaga (olatz.arrizabalaga@biodonostia.org); Moreno L., leire.moreno@biodonostia.org; Garrós L, laura.garros@biodonostia.org; Ayuso-Sacido A., Pollard SM., Belda-Iniesta C., Samprón N., Perona R., rperona@iib.uam.es; Matheu, A., ander.matheu@biodonostia.org


The MAPK phosphatase MKP1 (DUSP1) is overexpressed in many human cancers, including breast or lung cancers, but little is known about its implication in one of the most agressive human cancers: glioblastoma. Here, we report that MKP1 is overexpressed in a high number of glioblastoma patients and furthermore, these patients have a longer life-span as they are more sensitive to temozolomide, an important chemotheraputic treatment in this tumor. We found that MKP1 plays a critical role as it specifically regulates glioma stem cells by forcing them to enter into a differentiated state that make them less proliferative and chemotherapeutically more sensitive. Looking for a mechanism, it seems that MKP1 specifically targets p38 when overexpressed in glioma cells. When we directly target this protein with a pharmacological inhibitor (SB235080), we found the same phenotype as found with high-MKP1 levels. Moreover, high levels of MKP1 correlate with low levels of the stem cell marker SOX2, thus opening an interesting path in relation to cancer stem cells and treatment.

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