Chen Xueran, Li Hao, Fan Xiaoqing, Zhao Chenggang, Ye Kaiqin, Zhao Zhiyang, Hu Lizhu, Ma Huihui, Wang Hongzhi, Fang Zhiyou
Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui 230031, China.
Department of Molecular Pathology, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, ShuShan Hu Road, Hefei, Anhui 230031, China.
Mol Ther Oncolytics. 2020 May 22;17:518-530. doi: 10.1016/j.omto.2020.05.007. eCollection 2020 Jun 26.
Glioblastoma multiforme (GBM) almost invariably acquires an invasive phenotype, resulting in limited therapeutic options. Protein palmitoylation markedly affects tumorigenesis and malignant progression in GBM. The role of protein palmitoylation in GBM, however, has not been systematically reported. This study aimed to investigate the effect of protein palmitoylation on GBM cell survival and the cell cycle. In this study, most palmitoyltransferases were upregulated in GBM and its cell lines, and protein palmitoylation participated in signaling pathways controlling cell survival and the GBM cell cycle. Inhibition of protein palmitoylation with substrate-analog inhibitors, that is, 2-bromopalmitate, cerulenin, and tunicamycin, induced G cell cycle arrest and cell death in GBM cells through enhanced endoplasmic reticulum (ER) stress. These effects are primarily attributed to the palmitoylation inhibitors activating pro-apoptotic pathways and ER stress signals. Further analysis revealed was the accumulation of SUMOylated XBP1 (X-box binding protein 1) and its transcriptional repression, along with a reduction in XBP1 palmitoylation. Taken together, the present results indicate that protein palmitoylation plays an important role in the survival of GBM cells, further providing a potential therapeutic strategy for GBM.
多形性胶质母细胞瘤（GBM）几乎总是呈现侵袭性表型，导致治疗选择有限。蛋白质棕榈酰化显著影响GBM的肿瘤发生和恶性进展。然而，蛋白质棕榈酰化在GBM中的作用尚未得到系统报道。本研究旨在探讨蛋白质棕榈酰化对GBM细胞存活和细胞周期的影响。在本研究中，大多数棕榈酰转移酶在GBM及其细胞系中上调，并且蛋白质棕榈酰化参与了控制细胞存活和GBM细胞周期的信号通路。用底物类似物抑制剂（即2-溴棕榈酸酯、浅蓝菌素和衣霉素）抑制蛋白质棕榈酰化，通过增强内质网（ER）应激诱导GBM细胞的G期细胞周期停滞和细胞死亡。这些效应主要归因于棕榈酰化抑制剂激活促凋亡途径和ER应激信号。进一步分析发现，SUMO化的XBP1（X盒结合蛋白1）积累及其转录抑制，同时XBP1棕榈酰化减少。综上所述，目前的结果表明蛋白质棕榈酰化在GBM细胞存活中起重要作用，进一步为GBM提供了一种潜在的治疗策略。
