| Literature DB >> 31712311 |
Kenta Masui1, Mio Harachi2, Shiro Ikegami3, Huijun Yang3, Hiromi Onizuka2, William H Yong4,5, Timothy F Cloughesy4,5,6, Yoshihiro Muragaki7, Takakazu Kawamata7, Nobutaka Arai8, Takashi Komori9, Webster K Cavenee3,10, Paul S Mischel3,10,11, Noriyuki Shibata2.
Abstract
In cancer, aberrant growth factor receptor signaling reprograms cellular metabolism and global gene transcription to drive aggressive growth, but the underlying mechanisms are not well-understood. Here we show that in the highly lethal brain tumor glioblastoma (GBM), mTOR complex 2 (mTORC2), a critical core component of the growth factor signaling system, couples acetyl-CoA production with nuclear translocation of histone-modifying enzymes including pyruvate dehydrogenase and class IIa histone deacetylases to globally alter histone acetylation. Integrated analyses in orthotopic mouse models and in clinical GBM samples reveal that mTORC2 controls iron metabolisms via histone H3 acetylation of the iron-related gene promoter, promoting tumor cell survival. These results nominate mTORC2 as a critical epigenetic regulator of iron metabolism in cancer.Entities:
Keywords: acetyl coenzyme A (acetyl-CoA); glioblastoma; glucose metabolism; histone acetylation; iron metabolism; mammalian target of rapamycin (mTOR)
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Year: 2019 PMID： 31712311 PMCID： PMC6926466 DOI： 10.1074/jbc.RA119.011519
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157