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dc.contributor.authorHan, Mingzhien_US
dc.contributor.authorWang, Shuaien_US
dc.contributor.authorYang, Ningen_US
dc.contributor.authorWang, Xuen_US
dc.contributor.authorZhao, Wenboen_US
dc.contributor.authorSdik Saed, Halalaen_US
dc.contributor.authorDaubon, Thomasen_US
dc.contributor.authorHuang, Binen_US
dc.contributor.authorChen, Anjingen_US
dc.contributor.authorLi, Gangen_US
dc.contributor.authorMiletic, Hrvojeen_US
dc.contributor.authorThorsen, Fritsen_US
dc.contributor.authorBjerkvig, Rolfen_US
dc.contributor.authorLi, Xingangen_US
dc.contributor.authorWang, Jianen_US
dc.PublishedHan M, Wang S, Yang N, Wang X, Zhao, Sdik Saed H, et al Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma. EMBO Molecular Medicine. 2019;12:e10924eng
dc.description.abstractDysregulated cholesterol metabolism is a hallmark of many cancers, including glioblastoma (GBM), but its role in disease progression is not well understood. Here, we identified cholesterol 24‐hydroxylase (CYP46A1), a brain‐specific enzyme responsible for the elimination of cholesterol through the conversion of cholesterol into 24(S)‐hydroxycholesterol (24OHC), as one of the most dramatically dysregulated cholesterol metabolism genes in GBM. CYP46A1 was significantly decreased in GBM samples compared with normal brain tissue. A reduction in CYP46A1 expression was associated with increasing tumour grade and poor prognosis in human gliomas. Ectopic expression of CYP46A1 suppressed cell proliferation and in vivo tumour growth by increasing 24OHC levels. RNA‐seq revealed that treatment of GBM cells with 24OHC suppressed tumour growth through regulation of LXR and SREBP signalling. Efavirenz, an activator of CYP46A1 that is known to penetrate the blood–brain barrier, inhibited GBM growth in vivo. Our findings demonstrate that CYP46A1 is a critical regulator of cellular cholesterol in GBM and that the CYP46A1/24OHC axis is a potential therapeutic target.en_US
dc.publisherEMBO Presseng
dc.rightsAttribution CC BYeng
dc.subjectcholesterol homeostasiseng
dc.titleTherapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Author(s)
dc.source.journalEMBO Molecular Medicine
dc.relation.projectNorges forskningsråd: 563961

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