Downregulation of β-arrestin 1 suppresses glioblastoma cell malignant progression vis inhibition of Src signaling
Downregulation of β-arrestin 1 suppresses glioblastoma cell malignant progression vis inhibition of Src signaling
复制标题
β-arrestin 1 的下调通过抑制 Src 信号传导抑制胶质母细胞瘤细胞的恶性进展
DOI：
10.1016/j.yexcr.2017.04.023
复制
发表时间：
2017-08-01
影响因子：
3.7
通讯作者：
Yu, Chunjiang
中科院分区：
文献类型：
--
作者：
Lan, Tian;Wang, Haoran;Yu, Chunjiang
多形性胶质母细胞瘤（GBM）是世界上最常见的脑恶性肿瘤之一，通常与预后不良相关，但其侵袭性的机制仍不清楚。在这里，我们揭示了β-抑制蛋白1在GBM中过表达，并导致较差的结果。β-arrestin 1的敲低抑制GBM细胞的增殖、侵袭性和糖酵解，并且还增强替莫唑胺功效。此外，我们发现β-arrestin 1的敲低降低了Src的活性，并且Src信号传导的抑制在β-arrestin 1沉默介导的GBM恶性肿瘤的抑制中至关重要。最后，我们研究了β-arrestin 1敲低对异种移植模型的肿瘤生长和存活的影响，发现sh β-arrestin 1明显抑制体内GBM生长并导致小鼠更好的存活。综上所述，我们的研究结果表明，敲低β-arrestin 1可以通过抑制Src信号转导抑制GBM细胞增殖，侵袭和糖酵解。因此，靶向β-arrestin 1可能是GBM治疗的潜在治疗策略。
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 beta-arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown of beta-arrestin 1 suppressed the proliferation, invasiveness and glycolysis of GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that knockdown of beta-arrestin 1 decreased the activity of Src, and suppression of Src signaling was critically involved in beta-arrestin 1 silencing-mediated suppression of GBM malignancies. Finally, we investigated the effect of beta-arrestin 1 knockdown on the tumor growth and survival of xenograft models, and found that sh beta-arrestin 1 apparently inhibited GBM growth in vivo and resulted in better survival of mice. Taken together, our findings suggest that knockdown of beta-arrestin 1 can suppress GBM cell proliferation, invasion and glycolysis by inhibiting Src signaling. Thus, targeting beta-arrestin 1 may be a potential therapeutic strategy for GBM treatment.