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TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma.

Nature communications | 2017

Aberrant amplification and mutations of epidermal growth factor receptor (EGFR) are the most common oncogenic events in glioblastoma (GBM), but the mechanisms by which they promote aggressive pathogenesis are not well understood. Here, we determine that non-canonical histone signature acetylated H3 lysine 23 (H3K23ac)-binding protein tripartite motif-containing 24 (TRIM24) is upregulated in clinical GBM specimens and required for EGFR-driven tumorigenesis. In multiple glioma cell lines and patient-derived glioma stem cells (GSCs), EGFR signaling promotes H3K23 acetylation and association with TRIM24. Consequently, TRIM24 functions as a transcriptional co-activator and recruits STAT3, leading to stabilized STAT3-chromatin interactions and subsequent activation of STAT3 downstream signaling, thereby enhancing EGFR-driven tumorigenesis. Our findings uncover a pathway in which TRIM24 functions as a signal relay for oncogenic EGFR signaling and suggest TRIM24 as a potential therapeutic target for GBM that are associated with EGFR activation.

Pubmed ID: 29129908 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS093843
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS095634
  • Agency: NCI NIH HHS, United States
    Id: R21 CA209345
  • Agency: NCI NIH HHS, United States
    Id: T32 CA070085

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