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

• Published in: Nature communications Vol. 8; no. 1; pp. 1454 - 13
• Main Authors: Lv, Deguan, Li, Yanxin, Zhang, Weiwei, Alvarez, Angel A., Song, Lina, Tang, Jianming, Gao, Wei-Qiang, Hu, Bo, Cheng, Shi-Yuan, Feng, Haizhong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.11.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1922; 692/4028/67/1922; Aberration; Acetylation; Activation; Brain cancer; Brain tumors; Chromatin; Epidermal growth factor; Epidermal growth factor receptors; Glioblastoma; Glioma cells; Humanities and Social Sciences; Lysine; multidisciplinary; Mutation; Pathogenesis; Science; Science (multidisciplinary); Signaling; Stat3 protein; Stem cells; Transcription; Tumorigenesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01731-w

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. EGF receptor (EGFR) amplification and mutation are major drivers in glioma tumorigenesis but this mechanism is not well understood. Here, the authors show EGFR-upregulated H3K23ac binds TRIM24 which recruits STAT3, leading to activation of STAT3 signaling, enhancing EGFR-driven tumorigenesis.