TRIM59 promotes gliomagenesis by inhibiting tc45 dephosphorylation of STAT3

Youzhou Sang, Yanxin Li*, Lina Song, Angel A. Alvarez, Weiwei Zhang, Deguan Lv, Jianming Tang, Feng Liu, Zhijie Chang, Shigetsugu Hatakeyama, Bo Hu, Shi Yuan Cheng, Haizhong Feng

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 novel component of the EGFR/STAT3 signaling axis in the regulation of glioma tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1792-1804
Number of pages13
JournalCancer Research
Volume78
Issue number7
DOIs
StatePublished - Apr 1 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sang, Y., Li, Y., Song, L., Alvarez, A. A., Zhang, W., Lv, D., Tang, J., Liu, F., Chang, Z., Hatakeyama, S., Hu, B., Cheng, S. Y., & Feng, H. (2018). TRIM59 promotes gliomagenesis by inhibiting tc45 dephosphorylation of STAT3. Cancer Research, 78(7), 1792-1804. https://doi.org/10.1158/0008-5472.CAN-17-2774