HIG-2 promotes glioma stemness and radioresistance mediated by IGFBP2-rich microparticles in hypoxia

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ying Yang, Ting Sun, Xuefei Xue, Huiling Tan, Yanyan Li, Wei Yang
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Abstract

Hypoxia can weaken the efficacy of radiotherapy and decrease tumor immunogenicity leading to immune escape. Thus, a thorough understanding of the key signaling pathways regulated by hypoxia is vitally important to enhance the radiosensitivity and improve immunosuppressive microenvironment of glioma. In this study, we verified the crucial role of hypoxia-inducible gene 2 (HIG-2) in lipid droplet (LD) accumulation and demonstrated that HIG-2 binding to frizzled class receptor 10 (FZD10) activated Wnt/β-catenin signaling pathway and increased its downstream insulin-like growth factor binding protein 2 (IGFBP2) level in microparticles (MPs) derived from glioma stem cells (GSCs), leading to decreased radiosensitivity and immunogenicity of MPs-receiving cells via the cross-talk between GSCs and non-stem glioma cells (GCs). These findings suggest that HIG-2 may be a promising target in glioma radiotherapy and/or immunotherapy.

high -2促进缺氧条件下富含igfbp2微粒介导的胶质瘤干性和辐射抗性。
缺氧可削弱放疗效果,降低肿瘤免疫原性,导致免疫逃逸。因此,深入了解缺氧调控的关键信号通路对于增强胶质瘤的放射敏感性和改善免疫抑制微环境至关重要。在本研究中,我们验证了缺氧诱导基因2 (high -2)在脂滴(LD)积累中的关键作用,并证明high -2与卷曲类受体10 (FZD10)的结合激活了Wnt/β-catenin信号通路,并增加了其下游胰岛素样生长因子结合蛋白2 (IGFBP2)在胶质瘤干细胞(GSCs)衍生的微颗粒(MPs)中的水平。通过GSCs和非干细胞胶质瘤细胞(GCs)之间的串扰,导致mp接收细胞的放射敏感性和免疫原性降低。这些发现表明high -2可能是胶质瘤放疗和/或免疫治疗的一个有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
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