ムラガキ ヨシヒロ   MURAGAKI Yoshihiro
  村垣 善浩
   所属   研究施設 研究施設
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma.
掲載誌名 正式名:The Journal of biological chemistry
略  称:J Biol Chem
ISSNコード:1083351X/00219258
掲載区分国外
巻・号・頁 294(51),19740-19751頁
著者・共著者 MASUI Kenta†, HARACHI Mio, IKEGAMI Shiro, YANG Huijun, ONIZUKA Hiromi, YONG William H., CLOUGHSY Timothy F., MURAGAKI Yoshihiro, KAWAMATA Takakazu, ARAI Nobutaka, KOMORI Takashi, CAVENEE Webster K., MISCHEL Paul S., SHIBATA Noriyuki
発行年月 2019/12/20
概要 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.
DOI 10.1074/jbc.RA119.011519
PMID 31712311