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Outlining involvement of stem cell program in regulation of O6‐methylguanine DNA methyltransferase and development of temozolomide resistance in glioblastoma
Author(s) -
Chumakova Anastasia,
Lathia Justin D.
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14280
Subject(s) - temozolomide , o 6 methylguanine dna methyltransferase , methyltransferase , cancer research , cancer stem cell , stem cell , dna repair , progenitor cell , population , dna methyltransferase , biology , cell , glioblastoma , microbiology and biotechnology , dna , medicine , genetics , methylation , environmental health
Glioblastoma is a malignant brain tumor that inevitably develops resistance to standard of care drug temozolomide (TMZ) due to a population of cells called cancer stem cells (CSCs). These cells utilize progenitor cell signaling programs and develop robust DNA repair machinery. In this editorial highlight we focus on stem cell regulation of TMZ resistance and discuss findings of Happold et al . ([Happold C., 2017]) that outline direct transcriptional regulation of DNA repair enzyme O6‐methylguanine DNA methyltransferase (MGMT) in glioblastoma CSCs through NFkB activation. The authors found that cells cultured in CSC propagating conditions exhibit increase in MGMT expression when compared to adherent differentiated monolayer cells. This in turn increases resistance to standard of care drug temozolomide (TMZ) in these cells. NFkB activation was found to directly activate expression of MGMT in sphere cultured GBM CSC.