葡萄糖转运蛋白1（GLUT1）通过与激活的表皮生长因子受体（EGFR）结合并调节其下游信号通路，使肿瘤细胞对EGFR酪氨酸激酶抑制剂（EGFR-TKIs）敏感。
GLUT1 sensitizes tumor cells to EGFR-TKIs by binding with activated EGFR and regulating its downstream signaling pathways.
作者信息
Xie Zhangrong, Zhou Zhiqing, Chen Sijie, Li Yu, He Xiaoniu, Chen Guoan
机构信息
Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, SUSTech Homeostatic Medicine Institute, School of Medicine，Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University， Tongji Shanxi Hospital, Taiyuan, 030032, China.
出版信息
Cell Commun Signal. 2025 May 28;23(1):247. doi: 10.1186/s12964-025-02259-z.
BACKGROUND
We have previously demonstrated that GLUT1 can interact with phosphorylated EGFR and has an oncogenic role in lung cancer. Here, we aim to investigate their binding region and its signaling pathways.
METHODS
The AlphaFold 3 prediction, Co-immunoprecipitation, and Western blot were used to uncover the interaction conditions of GLUT1 and EGFR. The RNA-seq data was analyzed to evaluate the difference in signaling pathways between wild-type EGFR and activated mutated EGFR. The xenograft tumor model was established to determine the therapy effect of the combination of GLUT1 inhibitor BAY-876 and EGFR TKI Osimertinib.
RESULTS
We found that the interaction ability of GLUT1 and EGFR depended on the activation of EGFR. GLUT1 interacted with EGFRvIII (loss 2-7 exons) but not with EGFRvI (loss 1-16 exons), so GLUT1 interacts with EGFR in the EGFR extracellular transmembrane region. GLUT1 regulated EGFR downstream signaling pathways. GLUT1 inhibitor BAY-876 can sensitize tumor cells to EGFR TKI Osimertinib.
CONCLUSIONS
GLUT1 participates in tumor progression by interacting with phosphor-EGFR, suggesting that inhibition of the GLUT1-EGFR axis may be a potential therapeutic strategy for lung cancer treatment.
背景
我们之前已经证明葡萄糖转运蛋白1（GLUT1）可与磷酸化的表皮生长因子受体（EGFR）相互作用，并在肺癌中发挥致癌作用。在此，我们旨在研究它们的结合区域及其信号通路。
方法
使用AlphaFold 3预测、免疫共沉淀和蛋白质免疫印迹法来揭示GLUT1和EGFR的相互作用情况。分析RNA测序数据以评估野生型EGFR和激活型突变EGFR之间信号通路的差异。建立异种移植肿瘤模型以确定GLUT1抑制剂BAY-876与EGFR酪氨酸激酶抑制剂（TKI）奥希替尼联合使用的治疗效果。
结果
我们发现GLUT1和EGFR的相互作用能力取决于EGFR的激活。GLUT1与EGFRvIII（缺失第2 - 7外显子）相互作用，但不与EGFRvI（缺失第1 - 16外显子）相互作用，因此GLUT1在EGFR细胞外跨膜区域与EGFR相互作用。GLUT1调节EGFR下游信号通路。GLUT1抑制剂BAY-876可使肿瘤细胞对EGFR TKI奥希替尼敏感。
结论
GLUT1通过与磷酸化EGFR相互作用参与肿瘤进展，这表明抑制GLUT1-EGFR轴可能是肺癌治疗的一种潜在策略。
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