PDF(Pubmed)
Abstract：
Glioma is the most frequently diagnosed primary brain tumor and typically has a poor prognosis because of malignant proliferation and invasion. It is urgent to elucidate the mechanisms driving glioma tumorigenesis and develop novel treatments to address this deadly disease. Here, we first revealed that PDZK1 is expressed at high levels in gliomas. Promoter hypomethylation may cause high expression of PDZK1 in glioma. Knockdown of PDZK1 inhibits glioma cell proliferation and invasion in vitro. Mechanistically, further investigations revealed that the loss of PDZK1 expression by siRNA inhibited the activation of the AKT/mTOR signaling pathway, leading to cell cycle arrest and apoptosis. Clinically, high expression of PDZK1 predicts a poorer prognosis for glioma patients than low expression of PDZK1. Overall, our study revealed that PDZK1 acts as a novel oncogene in glioma by binding to AKT1 and maintaining the activation of the AKT/mTOR signaling pathway. Thus, PDZK1 may be a potential therapeutic target for glioma.
摘要：
胶质瘤是最常见的原发性脑肿瘤，通常由于恶性增殖和侵袭而预后不良。迫切需要阐明驱动神经胶质瘤肿瘤发生的机制，并开发新的治疗方法来解决这种致命的疾病。这里,我们首先发现PDZK1在胶质瘤中高水平表达。启动子低甲基化可能导致神经胶质瘤中PDZK1的高表达。PDZK1敲除抑制胶质瘤细胞增殖和侵袭。机械上,进一步的研究表明，siRNA导致的PDZK1表达缺失抑制了AKT/mTOR信号通路的激活，导致细胞周期停滞和凋亡。临床上,与PDZK1低表达相比,PDZK1高表达预示神经胶质瘤患者预后较差.总的来说,我们的研究表明,PDZK1通过与AKT1结合并维持AKT/mTOR信号通路的激活,在神经胶质瘤中起新的癌基因作用.因此，PDZK1可能是胶质瘤的潜在治疗靶点。
