In:
Molecular Oncology, Wiley, Vol. 12, No. 3 ( 2018-03), p. 406-420
Abstract:
Glioblastoma ( GBM ) ranks among the most lethal cancers, with current therapies offering only palliation. Inter‐ and intrapatient heterogeneity is a hallmark of GBM , with epigenetically distinct cancer stem‐like cells ( CSC s) at the apex. Targeting GSC s remains a challenging task because of their unique biology, resemblance to normal neural stem/progenitor cells, and resistance to standard cytotoxic therapy. Here, we find that the chromatin regulator, JmjC domain histone H3K36me2/me1 demethylase KDM 2B, is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM 2B function genetically or pharmacologically impaired the survival of patient‐derived primary glioblastoma cells through the induction of DNA damage and apoptosis, sensitizing them to chemotherapy. KDM 2B loss decreased the GSC pool, which was potentiated by coadministration of chemotherapy. Collectively, our results demonstrate KDM 2B is crucial for glioblastoma maintenance, with inhibition causing loss of GSC survival, genomic stability, and chemoresistance.
Type of Medium:
Online Resource
ISSN:
1574-7891
,
1878-0261
DOI:
10.1002/mol2.2018.12.issue-3
DOI:
10.1002/1878-0261.12174
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2322586-5
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