beta-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G(2)/M phase transition
beta-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G(2)/M phase transition
复制标题
beta-Arrestin 1 在神经激肽 1 受体介导的胶质母细胞瘤细胞增殖和 G(2)/M 期转变中具有重要作用
DOI：
10.1074/jbc.m116.770420
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Z
中科院分区：
文献类型：
--
作者：
Zhang Yi-Xin;Li Xiao-Fang;Hu Hui;Song Xiao-Yun;Li Jing-Yi;Miao Xiao-Kang;Zhou Tian-Xiong;Yang Wen-Le;Zhang Xiao-Wei;Mou Ling-Yun;Wang Rui;Zhang Yi-Xin;Li Xiao-Fang;Yuan Guo-Qiang;Hu Hui;Song Xiao-Yun;Li Jing-Yi;Miao Xiao-Kang;Zhou Tian-Xiong;Yang Wen-Le;Z
Glioblastoma is the most common malignant brain tumor and has a poor prognosis. Tachykinin receptor neurokinin-1 (NK1R) is a promising target in glioblastoma therapy because of its overexpression in human glioblastoma. NK1R agonists promote glioblastoma cell growth, whereas NK1R antagonists efficiently inhibit cell growth bothin vitroandin vivo. However, the molecular mechanisms involved in these effects are incompletely understood. β-Arrestins (ARRBs) serve as scaffold proteins and adapters to mediate intracellular signal transduction. Here we show that the ARRB1-mediated signaling pathway is essential for NK1-mediated glioblastoma cell proliferation. ARRB1 knockdown significantly inhibited NK1-mediated glioblastoma cell proliferation and induced G2/M phase cell cycle arrest. ARRB1 knockdown cells showed remarkable down-regulation of CDC25C/CDK1/cyclin B1 activity. We also demonstrated that ARRB1 mediated prolonged phosphorylation of ERK1/2 and Akt in glioblastoma cells induced by NK1R activation. ERK1/2 and Akt phosphorylation are involved in regulating CDC25C/CDK1/cyclin B1 activity. The lack of long-term ERK1/2 and Akt activation in ARRB1 knockdown cells was at least partly responsible for the delayed cell cycle progression and proliferation. Moreover, we found that ARRB1-mediated ERK1/2 and Akt phosphorylation regulated the transcriptional activity of both NF-κB and AP-1, which were involved in cyclin B1 expression. ARRB1 deficiency increased the sensitivity of glioblastoma cells to the treatment of NK1R antagonists. Taken together, our results suggest that ARRB1 plays an essential role in NK1R-mediated cell proliferation and G2/M transition in glioblastoma cells. Interference with ARRB1-mediated signaling via NK1R may have potential significance for therapeutic strategies targeting glioblastoma.
