P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker
Abstract Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a prot...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-11-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-024-00541-2 |
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| _version_ | 1850162514745098240 |
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| author | Zheng Yuan Hongbo Jing Yilin Deng Meichen Liu Tao Jiang Xiong Jin Weiwei Lin Yang Liu Jinlong Yin |
| author_facet | Zheng Yuan Hongbo Jing Yilin Deng Meichen Liu Tao Jiang Xiong Jin Weiwei Lin Yang Liu Jinlong Yin |
| author_sort | Zheng Yuan |
| collection | DOAJ |
| description | Abstract Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a protein disulfide isomerase, as a serum marker that maintains stemness in GSCs through the Wnt/β-catenin signaling pathway. Transcriptional silencing of P4HB induces apoptosis and diminishes stem cell-like characteristics in GSCs. Treatments with the chemical CCF624 or the China National Medical Products Administration (NMPA)-approved securinine significantly prolonged survival in patient-derived xenograft mouse models, underscoring P4HB’s potential as a therapeutic target and presenting an expedited path to clinical application through drug repurposing. Additionally, elevated P4HB levels in patient serum were found to correlate with disease progression, underscoring its utility as a biomarker and its promise for precision medicine. |
| format | Article |
| id | doaj-art-11099e2828e945fab12e52c0f078b2a9 |
| institution | OA Journals |
| issn | 2157-9024 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj-art-11099e2828e945fab12e52c0f078b2a92025-08-20T02:22:33ZengNature Publishing GroupOncogenesis2157-90242024-11-0113111210.1038/s41389-024-00541-2P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum markerZheng Yuan0Hongbo Jing1Yilin Deng2Meichen Liu3Tao Jiang4Xiong Jin5Weiwei Lin6Yang Liu7Jinlong Yin8Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityMedical Innovation Research Division of Chinese PLA General HospitalHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityHenan Institute of Medical and Pharmaceutical SciencesHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan UniversityAbstract Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a protein disulfide isomerase, as a serum marker that maintains stemness in GSCs through the Wnt/β-catenin signaling pathway. Transcriptional silencing of P4HB induces apoptosis and diminishes stem cell-like characteristics in GSCs. Treatments with the chemical CCF624 or the China National Medical Products Administration (NMPA)-approved securinine significantly prolonged survival in patient-derived xenograft mouse models, underscoring P4HB’s potential as a therapeutic target and presenting an expedited path to clinical application through drug repurposing. Additionally, elevated P4HB levels in patient serum were found to correlate with disease progression, underscoring its utility as a biomarker and its promise for precision medicine.https://doi.org/10.1038/s41389-024-00541-2 |
| spellingShingle | Zheng Yuan Hongbo Jing Yilin Deng Meichen Liu Tao Jiang Xiong Jin Weiwei Lin Yang Liu Jinlong Yin P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker Oncogenesis |
| title | P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker |
| title_full | P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker |
| title_fullStr | P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker |
| title_full_unstemmed | P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker |
| title_short | P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker |
| title_sort | p4hb maintains wnt dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker |
| url | https://doi.org/10.1038/s41389-024-00541-2 |
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