EZH2 Palmitoylation Mediated by ZDHHC5 in p53-Mutant Glioma Drives Malignant Development and Progression
EZH2 Palmitoylation Mediated by ZDHHC5 in p53-Mutant Glioma Drives Malignant Development and Progression
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p53 突变型胶质瘤中 ZDHHC5 介导的 EZH2 棕榈酰化驱动恶性发展和进展
DOI：
10.1158/0008-5472.can-17-1139
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发表时间：
2017-09-15
期刊：
影响因子：
11.2
通讯作者：
Fang, Zhiyou
中科院分区：
文献类型：
--
作者：
Chen, Xueran;Ma, Huihui;Fang, Zhiyou
在30%的胶质瘤患者中发生突变p53的胶质瘤表现出治疗抗性和不良结局。在这项研究中，我们确定了突变型p53驱动癌细胞存活和恶性生长的新机制。我们记录了锌指蛋白ZDHHC 5在胶质瘤中的过表达，与正常脑组织相比，这一事件与p53突变密切相关。机制研究表明，突变p53转录上调ZDHHC 5沿着核转录因子NF-Y。这些事件通过改变肿瘤抑制因子EZH 2的棕榈酰化和磷酸化状态，促进胶质瘤干细胞样细胞的自我更新能力和致瘤性，从而促进胶质瘤的发展。总之，我们的工作突出了ZDHHC 5作为管理p53突变胶质瘤的候选治疗靶点。(C)2017年AACR。
Gliomas with mutant p53 occurring in 30% of glioma patients exhibit therapeutic resistance and poor outcomes. In this study, we identify a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. We documented overexpression of the zinc finger protein ZDHHC5 in glioma compared with normal brain tissue and that this event tightly correlated with p53 mutations. Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2. Taken together, our work highlighted ZDHHC5 as a candidate therapeutic target for management of p53- mutated gliomas. (C) 2017 AACR.