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MURAGAKI Yoshihiro
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Visiting Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma. |
| Journal | Formal name：The Journal of biological chemistry Abbreviation：J Biol Chem ISSN code：1083351X/00219258 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 294(51),pp.19740-19751 |
| Author and coauthor | 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 |
| Publication date | 2019/12/20 |
| Summary | 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 |