2. Academic Validation
  3. Protein Palmitoylation Regulates Cell Survival by Modulating XBP1 Activity in Glioblastoma Multiforme

Protein Palmitoylation Regulates Cell Survival by Modulating XBP1 Activity in Glioblastoma Multiforme

  • Mol Ther Oncolytics. 2020 May 22;17:518-530. doi: 10.1016/j.omto.2020.05.007.
Xueran Chen 1 2,  Hao Li 3,  Xiaoqing Fan 4 5,  Chenggang Zhao 1 3,  Kaiqin Ye 1 2,  Zhiyang Zhao 1 3,  Lizhu Hu 1 3,  Huihui Ma 6,  Hongzhi Wang 1 2,  Zhiyou Fang 1 2
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Molecular Pathology, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, ShuShan Hu Road, Hefei, Anhui 230031, China.
  • 3 School of Life Sciences, University of Science and Technology of China, No. 96, JinZhai Road, Hefei, Anhui 230026, China.
  • 4 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), No. 17, Lujiang Road, Hefei, Anhui 230001, China.
  • 5 Department of Anesthesiology, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei, Anhui 230001, China.
  • 6 Department of Radiation Oncology, First Affiliated Hospital, Anhui Medical University, No. 218, JiXi Road, Hefei, Anhui 230031, China.
PMID: 33024813 DOI: 10.1016/j.omto.2020.05.007
Abstract

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 G2 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.

Keywords

X-box binding protein 1; endoplasmic reticulum stress response; glioblastoma multiforme; palmitoyltransferases; protein palmitoylation.

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