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ShanghaiTech University Knowledge Management System
Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation | |
2025-01-11 | |
发表期刊 | CELL REPORTS (IF:7.5[JCR-2023],8.5[5-Year]) |
ISSN | 2211-1247 |
卷号 | 44期号:1页码:115142 |
发表状态 | 已发表 |
DOI | 10.1016/j.celrep.2024.115142 |
摘要 | Glioblastoma (GBM) is a highly lethal malignant brain tumor with poor survival rates, and chemoresistance poses a significant challenge to the treatment of patients with GBM. Here, we show that transketolase (TKT), a metabolic enzyme in the pentose phosphate pathway (PPP), attenuates the chemotherapy sensitivity of glioma cells in a manner independent of catalytic activity. Mechanistically, chemotherapeutic drugs can facilitate the translocation of TKT protein from the cytosol into the nucleus, where TKT physically interacts with XRN2 to regulate the resolution and removal of R-loops. Depletion of TKT leads to increased R-loop accumulation and genome instability, increasing the susceptibility of glioma cells to chemotherapy. In conclusion, our study reveals a non-metabolic function of TKT in regulating R-loop dynamics, genome instability, and chemotherapy sensitivity in gliomas. |
关键词 | CP: Cancer R-loops TKT chemotherapy sensitivity glioma |
URL | 查看原文 |
收录类别 | SCI ; SCIE |
语种 | 英语 |
资助项目 | Noncommunicable Chronic Diseases-National Science and Technology Major Project[2023ZD0500400] ; National Natural Science Foundation of China["82473174","82103376","824B200044"] ; CAMS Innovation Fund for Medical Sciences (CIFMS)["2022-I2M-C","T -B-112"] ; National Key R&D Program of China["2022YFC2406703","2022YFC3401600","2023YFC2510000"] |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:001410443900001 |
出版者 | CELL PRESS |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/467899 |
专题 | 免疫化学研究所_特聘教授组_刘海坤组 生命科学与技术学院_博士生 |
共同第一作者 | Hao Xu |
通讯作者 | Dan Ye; Ying Mao; Wei Hua |
作者单位 | 1.Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; 2.Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. 3.Shanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai 201210, China. 4.Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), and Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: yedan@fudan.edu.cn. 5.Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; National Center for Neurological Disorders, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai 200040, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China. Electronic address: maoying@fudan.edu.cn. 6.Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; National Center for Neurological Disorders, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai 200040, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China. Electronic address: drhuawei@fudan.edu.cn. |
推荐引用方式 GB/T 7714 | Minjie Fu,Mengli Zhang,Licheng Zhang,et al. Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation[J]. CELL REPORTS,2025,44(1):115142. |
APA | Minjie Fu.,Mengli Zhang.,Licheng Zhang.,Yuan Feng.,Chao Gao.,...&Wei Hua.(2025).Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation.CELL REPORTS,44(1),115142. |
MLA | Minjie Fu,et al."Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation".CELL REPORTS 44.1(2025):115142. |
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