期刊
CANCER RESEARCH
卷 78, 期 7, 页码 1792-1804出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-17-2774
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资金
- National Natural Science Foundation of China [81372704, 81572467, 81470315, 81772663]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning [2014024]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161310]
- New Hundred Talent Program (Outstanding Academic Leader) at Shanghai Municipal Health Bureau [2017BR021]
- Technology Transfer Project of Science AMP
- Technology Dept. at Shanghai Jiao Tong University School of Medicine [ZT201701]
- Shanghai Jiao Tong University Medical Engineering Cross Fund [YG2017MS32]
- US NIH [NS093843, NS95634, CA209345]
- NIH/NCI training grant [T32 CA070085]
- NIH LRP award [L32 MD010147]
- JSPS [24112006, 15H04690]
- Grants-in-Aid for Scientific Research [15H04690, 24112006] Funding Source: KAKEN
Aberrant EGFR signaling is a common driver of glioblastoma (GBM) pathogenesis; however, the downstream effectors that sustain this oncogenic pathway remain unclarified. Here we demonstrate that tripartite motif-containing protein 59 (TRIM59) acts as a new downstream effector of EGFR signaling by regulating STAT3 activation in GBM. EGFR signaling led to TRIM59 upregulation through SOX9 and enhanced the interaction between TRIM59 and nuclear STAT3, which prevents STAT3 dephosphorylation by the nuclear form of T-cell protein tyrosine phosphatase (TC45), thereby maintaining transcriptional activation and promoting tumorigenesis. Silencing TRIM59 suppresses cell proliferation, migration, and orthotopic xenograft brain tumor formation of GBM cells and glioma stem cells. Evaluation of GBM patient samples revealed an association between EGFR activation, TRIM59 expression, STAT3 phosphorylation, and poor prognoses. Our study identifies TRIM59 as a new regulator of oncogenic EGFR/STAT3 signaling and as a potential therapeutic target for GBM patients with EGFR activation. Significance: These findings identify a novomponent of the EGFR/STAT3 signaling axis in the regulation of glioma tel cumorigenesis. (C) 2018 AACR.
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