Histone acetyltransferase KAT6A upregulates PI3K/AKT signaling through TRIM24 binding

Deguan Lv, Feng Jia, Yanli Hou, Youzhou Sang, Angel A. Alvarez, Weiwei Zhang, Wei Qiang Gao, Bo Hu, Shi Yuan Cheng, Jianwei Ge*, Yanxin Li, Haizhong Feng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here, we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM), where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation, and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis. Overexpressing activated AKT or PIK3CA rescued the growth inhibition due to KAT6A silencing. Conversely, the pan-PI3K inhibitor LY294002 abrogated the growth-promoting effect of KAT6A. Overexpression of KAT6A or TRIM24, but not KAT6A acetyltransferase activity–deficient mutants or TRIM24 mutants lacking H3K23ac-bind-ing sites, promoted PIK3CA expression, AKT phosphorylation, and cell proliferation. Taken together, our results define an essential role of KAT6A in glioma formation, rationalizing its candidacy as a therapeutic target for GBM treatment.

Original languageEnglish (US)
Pages (from-to)6190-6201
Number of pages12
JournalCancer Research
Issue number22
StatePublished - Nov 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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