ArticleNature communications2025
Combined targeting of glioblastoma stem cells of different cellular states disrupts malignant progression.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
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Who cites it
30 citing papers in PubMed.
- Targeting LDHA Palmitoylation Sensitizes GBM to Chemoradiotherapy via Suppressing Palmitic Acid Induced Glycolytic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dysregulated mScience advances · 2026Article
- Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of NR2F2-mediated reprogramming of endothelial cells in glioblastoma progression.iScience · 2026Article
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- Ferroptosis with Contributions from Apoptosis and Necroptosis in Porphyrazine III-Based Photodynamic Therapy of Primary Human Gliomas.Pharmaceutics · 2026Article
- Integrating Molecular Pathology, Tumor Microenvironment, and Novel Therapies to Overcome Resistance in Glioblastoma.Journal of molecular neuroscience : MN · 2026Review
- Leveraging single-cell and spatial omics for brain tumour insights to improve therapeutic strategies.Molecular brain · 2026Review
- Localized delivery of hyaluronic acid-doxorubicin from a surgical paste for post-operative glioblastoma treatment.Materials today. Bio · 2026Article
- Computational design and immunoinformatics validation of a T cell multi-epitope vaccine targeting glioblastoma stem cells.Scientific reports · 2026Article
- Exosomal NEAT1 from tumor stem cells induces SIRPAJournal of experimental & clinical cancer research : CR · 2026Article
- Review
- Article
- Glioblastoma Multiforme: Current Developments in Molecular Pathways, Magnetic Field-Based Interventions, and Personalized Therapy.Journal of clinical practice and research · 2026Review
- Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dissociable perfusion chip (DPC): perfusable microfluidic chip for single-cell screening of anti-cancer drugs in live glioblastoma explants.Lab on a chip · 2026Article
- Review
- Review
- Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in glioblastoma.iScience · 2026Article
- From Data to Decision: Integrating Bioinformatics into Glioma Patient Stratification and Immunotherapy Selection.International journal of molecular sciences · 2026Review
Corrections and comments
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Authors and funding
47 authors.
Chenfei Lu *Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Tao Kang *Department of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Junxia Zhang *Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Kailin Yang *Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.
Yang Liu *Department of Pharmacology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Kefan SongDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Qiankun LinDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Deobrat DixitUniversity of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.
Ryan C GimpleDepartment of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-7189-3243
Qian ZhangDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Zhumei ShiDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Xiao FanDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Qiulian WuUniversity of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.
Daqi LiDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0002-7448-7435
Danyang ShanDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Jiancheng GaoDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Danling GuDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Hao YouDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Yangqing LiDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Junlei YangDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Linjie ZhaoUniversity of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-3372-2873
Zhixin QiuDepartment of Anesthesiology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Hui YangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-2865-5311
Ningwei ZhaoAffiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Wei GaoDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0002-7889-1662
Weiwei TaoCollege of Biomedicine and Health & College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.ORCID http://orcid.org/0000-0003-2933-9262
Yingmei LuDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0003-3187-4344
Yun ChenDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0002-4118-362X
Jing JiDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0002-7372-024X
Zhe ZhuDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5385-948X
Chunsheng KangLaboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.ORCID http://orcid.org/0000-0002-3255-3369
Jianghong ManState Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.ORCID http://orcid.org/0000-0001-6020-3537
Sameer AgnihotriUniversity of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-6584-3795
Qianghu WangInstitute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0002-3488-1059
Fan LinDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Xu QianInstitute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0003-1533-8568
Stephen C MackDepartment of Developmental Neurobiology, Neurobiology and Brain Tumor Program, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-9620-4742
Zhibin HuInstitute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0002-8277-5234
Chaojun LiInstitute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0001-9474-7321
Michael D TaylorDepartment of Pediatrics- Hematology/Oncology and Neurosurgery, Texas Children's Cancer Center, Hematology-Oncology Section, Baylor College of Medicine, Houston, Texas, USA.ORCID http://orcid.org/0000-0001-7009-3466
Ning LiuDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Nu ZhangDepartment of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.ORCID http://orcid.org/0000-0002-2817-7065
Ming LuDepartment of Cell Biology, National Health Commission Key Laboratory of Antibody Techniques, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0001-8018-8389
Yongping YouDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. yypl9@njmu.edu.cn.
Jeremy N RichUniversity of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA. drjeremyrich@gmail.com.ORCID http://orcid.org/0000-0001-7845-5302
Wei ZhangDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. zhangwei_vincent@126.com.ORCID http://orcid.org/0000-0001-7800-3189
Xiuxing WangDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. drxiuxingwang@163.com.ORCID http://orcid.org/0000-0001-7115-729X
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most lethal primary brain tumor with intra-tumoral hierarchy of glioblastoma stem cells (GSCs). The heterogeneity of GSCs within GBM inevitably leads to treatment resistance and tumor recurrence. Molecular mechanisms of different cellular state GSCs remain unclear. Here, we find that classical (CL) and mesenchymal (MES) GSCs are enriched in reactive immune region and high CL-MES signature informs poor prognosis in GBM. Through integrated analyses of GSCs RNA sequencing and single-cell RNA sequencing datasets, we identify specific GSCs targets, including MEOX2 for the CL GSCs and SRGN for the MES GSCs. MEOX2-NOTCH and SRGN-NFκB axes play important roles in promoting proliferation and maintaining stemness and subtype signatures of CL and MES GSCs, respectively. In the tumor microenvironment, MEOX2 and SRGN mediate the resistance of CL and MES GSCs to macrophage phagocytosis. Using genetic and pharmacologic approaches, we identify FDA-approved drugs targeting MEOX2 and SRGN. Combined CL and MES GSCs targeting demonstrates enhanced efficacy, both in vitro and in vivo. Our results highlighted a therapeutic strategy for the elimination of heterogeneous GSCs populations through combinatorial targeting of MEOX2 and SRGN in GSCs.
Indexed as
Brain NeoplasmsGlioblastomaNeoplastic Stem CellsAnimalsCell Line, TumorCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceNF-kappa BReceptors, NotchTumor MicroenvironmentXenograft Model Antitumor AssaysNF-kappa BReceptors, Notch
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