Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation
Summary: 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 ch...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724014931 |
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| author | Minjie Fu Mengli Zhang Licheng Zhang Yuan Feng Chao Gao Hao Xu Jinsen Zhang Huaichao Zhang Tianping Peng Youjun Chu Yonghe Wu Pu Wang Dan Ye Ying Mao Wei Hua |
| author_facet | Minjie Fu Mengli Zhang Licheng Zhang Yuan Feng Chao Gao Hao Xu Jinsen Zhang Huaichao Zhang Tianping Peng Youjun Chu Yonghe Wu Pu Wang Dan Ye Ying Mao Wei Hua |
| author_sort | Minjie Fu |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-a6b9ba3b72ee485c8abc1fd39c40f71c |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-a6b9ba3b72ee485c8abc1fd39c40f71c2025-01-11T06:41:12ZengElsevierCell Reports2211-12472025-01-01441115142Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formationMinjie Fu0Mengli Zhang1Licheng Zhang2Yuan Feng3Chao Gao4Hao Xu5Jinsen Zhang6Huaichao Zhang7Tianping Peng8Youjun Chu9Yonghe Wu10Pu Wang11Dan Ye12Ying Mao13Wei Hua14Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaShanghai 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai 201210, ChinaShanghai 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, ChinaDepartment 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; Corresponding authorDepartment 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; Corresponding authorDepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724014931CP: Cancer |
| spellingShingle | Minjie Fu Mengli Zhang Licheng Zhang Yuan Feng Chao Gao Hao Xu Jinsen Zhang Huaichao Zhang Tianping Peng Youjun Chu Yonghe Wu Pu Wang Dan Ye Ying Mao Wei Hua Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation Cell Reports CP: Cancer |
| title | Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation |
| title_full | Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation |
| title_fullStr | Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation |
| title_full_unstemmed | Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation |
| title_short | Transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating R-loop formation |
| title_sort | transketolase attenuates the chemotherapy sensitivity of glioma cells by modulating r loop formation |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724014931 |
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