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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])
ISSN2211-1247
卷号44期号:1页码:115142
发表状态已发表
DOI10.1016/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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