@article{87ffd719b8fa416182699220bab6af6d,
title = "Reduced expression of proteolipid protein 2 increases ER stress-induced apoptosis and autophagy in glioblastoma",
abstract = "Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high-grade gliomas than in low-grade gliomas. We confirmed these results at the protein level through IHC staining of high-grade (n = 56) and low-grade glioma biopsies (n = 16). Kaplan-Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87- and U251-siPLP2 cells. Finally, intracranial xenografts derived from U87- and U251-shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target.",
keywords = "ER stress, apoptosis, autophagy, glioblastoma, proteolipid protein 2",
author = "Zichao Feng and Wenjing Zhou and Jiwei Wang and Qichao Qi and Mingzhi Han and Yang Kong and Yaotian Hu and Yulin Zhang and Anbin Chen and Bin Huang and Anjing Chen and Di Zhang and Wenjie Li and Qing Zhang and Rolf Bjerkvig and Jian Wang and Frits Thorsen and Xingang Li",
note = "Funding Information: This work was supported by the National Natural Science Foundation of China (81972351, 81701329 and 81702474), the Department of Science & Technology of Shandong Province (2017CXGC1502, 2017CXGC1504 and 2018GSF118082), the Special Foundation for Taishan Scholars (ts20110814, tshw201502056 and tsqn20161067), the Shandong Provincial Natural Science Foundation (ZR2017MH116 and ZR2017MH015), the China Postdoctoral Science Foundation (2018M642666), the Jinan Science and Technology Bureau of Shandong Province (201704096), Stiftelsen Kristian Gerhard Jebsen, Helse‐Vest, Haukeland Hospital, the University of Bergen, the Norwegian Cancer Society and the Norwegian Research Council. Funding Information: This work was supported by the National Natural Science Foundation of China (81972351, 81701329 and 81702474), the Department of Science & Technology of Shandong Province (2017CXGC1502, 2017CXGC1504 and 2018GSF118082), the Special Foundation for Taishan Scholars (ts20110814, tshw201502056 and tsqn20161067), the Shandong Provincial Natural Science Foundation (ZR2017MH116 and ZR2017MH015), the China Postdoctoral Science Foundation (2018M642666), the Jinan Science and Technology Bureau of Shandong Province (201704096), Stiftelsen Kristian Gerhard Jebsen, Helse-Vest, Haukeland Hospital, the University of Bergen, the Norwegian Cancer Society and the Norwegian Research Council. Publisher Copyright: {\textcopyright} 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.",
year = "2020",
month = mar,
day = "1",
doi = "10.1111/jcmm.14840",
language = "English",
volume = "24",
pages = "2847--2856",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",
}