Lan Tian, Wang Haoran, Zhang Zhihua, Zhang Mingshan, Qu Yanming, Zhao Zitong, Fan Xinyi, Zhan Qimin, Song Yongmei, Yu Chunjiang
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China; State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Exp Cell Res. 2017 Aug 1;357(1):51-58. doi: 10.1016/j.yexcr.2017.04.023. Epub 2017 Apr 22.
Glioblastoma multiforme (GBM) is one of the most common brain malignancies worldwide and is typically associated with a dismal prognosis, yet the mechanisms underlying its aggressiveness remain unclear. Here, we revealed that β-arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown of β-arrestin 1 suppressed the proliferation, invasiveness and glycolysis of GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that knockdown of β-arrestin 1 decreased the activity of Src, and suppression of Src signaling was critically involved in β-arrestin 1 silencing-mediated suppression of GBM malignancies. Finally, we investigated the effect of β-arrestin 1 knockdown on the tumor growth and survival of xenograft models, and found that shβ-arrestin 1 apparently inhibited GBM growth in vivo and resulted in better survival of mice. Taken together, our findings suggest that knockdown of β-arrestin 1 can suppress GBM cell proliferation, invasion and glycolysis by inhibiting Src signaling. Thus, targeting β-arrestin 1 may be a potential therapeutic strategy for GBM treatment.
多形性胶质母细胞瘤（GBM）是全球最常见的脑恶性肿瘤之一，通常预后不佳，但其侵袭性背后的机制仍不清楚。在此，我们揭示β-抑制蛋白1在GBM中过表达，并导致较差的预后。敲低β-抑制蛋白1可抑制GBM细胞的增殖、侵袭和糖酵解，还可增强替莫唑胺的疗效。此外，我们发现敲低β-抑制蛋白1可降低Src的活性，而抑制Src信号通路关键参与了β-抑制蛋白1沉默介导的GBM恶性肿瘤抑制作用。最后，我们研究了敲低β-抑制蛋白1对异种移植模型肿瘤生长和存活的影响，发现shβ-抑制蛋白1明显抑制体内GBM生长，并使小鼠存活时间延长。综上所述，我们的研究结果表明，敲低β-抑制蛋白1可通过抑制Src信号通路来抑制GBM细胞的增殖、侵袭和糖酵解。因此，靶向β-抑制蛋白1可能是GBM治疗的一种潜在治疗策略。
