Song Hai, Wang Yanpei, Shi Chaojia, Lu Jianxiang, Yuan Tian, Wang Xiangpeng
Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Oncol. 2021 Feb 11;10:583984. doi: 10.3389/fonc.2020.583984. eCollection 2020.
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 and xenograft tumors growth . 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.
胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的脑肿瘤。表皮生长因子受体（EGFR）的过表达或激活在多种人类癌症中普遍存在，并促进肿瘤发生。然而，EGFR异常激活的潜在分子机制及其下游信号通路在很大程度上仍不清楚。在本研究中，我们报告SH3结构域激酶结合蛋白1（SH3KBP1）的mRNA和蛋白水平在GBM中高表达，其高表达与胶质瘤患者较差的生存率相关。此外，我们提供证据表明SH3KBP1在GBM干细胞（GSCs）中显著表达，并有潜力作为一种新型的GSCs标志物。此外，沉默SH3KBP1会显著损害GBM细胞的增殖、迁移以及GSCs的自我更新能力和异种移植肿瘤的生长。最重要的是，我们发现SH3KBP1直接与EGFR相互作用，并可能作为一种衔接蛋白来转导EGFR信号。总之，我们的工作揭示了SH3KBP1是致癌EGFR信号的一种新型调节因子，也是EGFR激活的GBM患者的潜在治疗靶点。
