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Author Notes:

Correspondence: D. J. Brat, Department of Pathology and Laboratory Medicine, Emory University Hospital, H‐195 1364 Clifton Rd. NE. Atlanta, GA 30322, USA Tel: 404 712 1266 E‐mail: dbrat@emory.edu

CZ, SM, and DJB involved in conception and design and in analysis and interpretation of data.

CZ, SM, CTB, JLR, MJC, JK, and DJB involved in data acquisition and in writing and reviewing of the manuscript.

CZ, SM, and CTB involved in development of methodology.

CTB and DJB provided administrative, technical, or material support.

CZ and DJB supervised the study.

The authors thank Dr. Kai‐Ming Xu, Dr. Dong Chen, Dr. Bing Yu, Dr. Zhixiong Liu, Dr. Bin Jiao, and Dr. Bin Wang for providing useful technical advice and helpful comments on this manuscript.

The authors thank Dr. Edmund K. Waller and Dr. Ernestine A. Mahar for advice and guidance in flow cytometry using BD Canto II and Aria instruments.

The authors also thank Department of Pediatrics Flow Cytometer Core, the Winship Cancer Tissue and Pathology Shared Resource, and the Integrated Cellular Imaging Shared Resource.


Research Funding:

This work was supported by US Public Health Service National Institutes of Health (NIH) Grants R01 CA176659 (DJB), CA149107 (DJB), and K25CA181503 (JK); the Winship Cancer Institute NCI Cancer Center Support Grant P30CA138292; and the Georgia Research Alliance (DJB).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • glioblastoma
  • PIAS3
  • STAT3
  • stem cell
  • TRIM8

TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3


Journal Title:

Molecular Oncology


Volume 11, Number 3


, Pages 280-294

Type of Work:

Article | Final Publisher PDF


Glioblastoma (GBM) is the most malignant form of primary brain tumor, and GBM stem-like cells (GSCs) contribute to the rapid growth, therapeutic resistance, and clinical recurrence of these fatal tumors. STAT3 signaling supports the maintenance and proliferation of GSCs, yet regulatory mechanisms are not completely understood. Here, we report that tri-partite motif-containing protein 8 (TRIM8) activates STAT3 signaling to maintain stemness and self-renewing capabilities of GSCs. TRIM8 (also known as 'glioblastoma-expressed ring finger protein') is expressed equally in GBM and normal brain tissues, despite its hemizygous deletion in the large majority of GBMs, and its expression is highly correlated with stem cell markers. Experimental knockdown of TRIM8 reduced GSC self-renewal and expression of SOX2, NESTIN, and p-STAT3, and promoted glial differentiation. Overexpression of TRIM8 led to higher expression of p-STAT3, c-MYC, SOX2, NESTIN, and CD133, and enhanced GSC self-renewal. We found that TRIM8 activates STAT3 by suppressing the expression of PIAS3, an inhibitor of STAT3, most likely through E3-mediated ubiquitination and proteasomal degradation. Interestingly, we also found that STAT3 activation upregulates TRIM8, providing a mechanism for normalized TRIM8 expression in the setting of hemizygous gene deletion. These data demonstrate that bidirectional TRIM8-STAT3 signaling regulates stemness in GSC.

Copyright information:

© 2017 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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