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  • mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma.

mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma.

The Journal of biological chemistry (2019-11-13)
Kenta Masui, Mio Harachi, Shiro Ikegami, Huijun Yang, Hiromi Onizuka, William H Yong, Timothy F Cloughesy, Yoshihiro Muragaki, Takakazu Kawamata, Nobutaka Arai, Takashi Komori, Webster K Cavenee, Paul S Mischel, Noriyuki Shibata
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.

MATERIALS
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Anti-EGFR (Ab-1070) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)