期刊
FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.583984
关键词
glioblastoma; SH3KBP1; epidermal growth factor receptor; adaptor; glioblastoma stem cells
类别
资金
- Health Commission of Yunnan Province Training plan for Medical Reserve Talents [H-2017029]
- Yunnan Health Science and Technology Project (internal organization) [2017NS058]
- Research Innovation team of Yunnan province [2019HC022]
- Yunnan clinical medical center of nervous system diseases [ZX2019-03-05]
This study reveals that SH3KBP1 is highly expressed in GBM and associated with worse survival outcomes, potentially serving as a marker for GSCs. Silencing SH3KBP1 can significantly impair GBM cell proliferation, migration, and GSCs self-renewal, likely acting as an adaptor protein for EGFR signaling.
Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Overexpression or activation of epidermal growth factor receptor (EGFR) occurs commonly in multiple human cancers and promotes tumorigenesis. However, the underlying molecular mechanism of EGFR aberrant activation and the downstream signaling pathways remains largely unknown. In this study, we report that both SH3-domain kinase binding protein 1 (SH3KBP1) mRNA and protein levels are highly expressed in GBM and its high expression is associated with worse survival of glioma patients. In addition, we provide evidence that SH3KBP1 is prominently expressed in GBM stem cells (GSCs) and have potential to serve as a novel GSCs marker. Moreover, silencing SH3KBP1 dramatically impairs GBM cell proliferation, migration and GSCs self-renewal ability in vitro and xenograft tumors growth in vivo. Most importantly, we found that SH3KBP1 directly interacts with EGFR and may act as an adaptor protein to transduce EGFR signaling. Together, our work uncovers SH3KBP1 as a novel regulator of oncogenic EGFR signaling and also as a potential therapeutic target for GBM patients with EGFR activation.
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