Scholarlink

<p>Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis due to its resistance to radiotherapy. Epidermal growth factor receptor variant III (EGFRvIII), a common mutation in GBM, promotes radioresistance through ligand-independent activation. We hypothesized that membrane flexibility influences EGFRvIII activation and enhances resistance. Bone marrow stromal antigen 2 (BST2, CD317, or TETHERIN) was identified as a key mediator linking membrane dynamics to EGFRvIII-driven survival signaling. Radiation-induced changes in membrane flexibility amplified BST2 activity, stabilizing lipid rafts and promoting EGFRvIII clustering. Pharmacological inhibition of BST2 with arbutin, an FDA-approved compound, disrupted this mechanism, increasing GBM radiosensitivity by enhancing mitochondrial reactive oxygen species (ROS) production and apoptosis. Additionally, BST2 downregulation impaired de novo lipogenesis and reduced lipid droplet accumulation, highlighting its role in metabolic reprogramming. In orthotopic xenograft models, BST2 inhibition suppressed tumor growth and prolonged survival. These findings establish BST2 as a key regulator of membrane-driven radioresistance in GBM. Targeting BST2-mediated membrane remodeling may provide a novel therapeutic strategy to enhance radiotherapy efficacy.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Membrane flexibility induced by BST2 contributes to radioresistance in glioblastoma

  • 期刊论文

  • 发表日期：

    2025年8月18日

查看全文
  • Haksoo Lee,
  • Dahye Kim,
  • Byeongsoo Kim,
  • Eunguk Shin,
  • Hyunkoo Kang,
  • Jae-Myung Lee,
  • HyeSook Youn,
  • BuHyun Youn

摘要

Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis due to its resistance to radiotherapy. Epidermal growth factor receptor variant III (EGFRvIII), a common mutation in GBM, promotes radioresistance through ligand-independent activation. We hypothesized that membrane flexibility influences EGFRvIII activation and enhances resistance. Bone marrow stromal antigen 2 (BST2, CD317, or TETHERIN) was identified as a key mediator linking membrane dynamics to EGFRvIII-driven survival signaling. Radiation-induced changes in membrane flexibility amplified BST2 activity, stabilizing lipid rafts and promoting EGFRvIII clustering. Pharmacological inhibition of BST2 with arbutin, an FDA-approved compound, disrupted this mechanism, increasing GBM radiosensitivity by enhancing mitochondrial reactive oxygen species (ROS) production and apoptosis. Additionally, BST2 downregulation impaired de novo lipogenesis and reduced lipid droplet accumulation, highlighting its role in metabolic reprogramming. In orthotopic xenograft models, BST2 inhibition suppressed tumor growth and prolonged survival. These findings establish BST2 as a key regulator of membrane-driven radioresistance in GBM. Targeting BST2-mediated membrane remodeling may provide a novel therapeutic strategy to enhance radiotherapy efficacy.