ArticleNeuro-oncology2014
JAK2/STAT3 targeted therapy suppresses tumor invasion via disruption of the EGFRvIII/JAK2/STAT3 axis and associated focal adhesion in EGFRvIII-expressing glioblastoma.
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Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 93 citations in OpenAlex.
- Repurposing T-type calcium channel blocker lomerizine as a therapeutic strategy for glioblastoma.JCI insight · 2026Article
- NIBAN2 Stimulates Glioma Growth by Regulating the JAK2/STAT3/c-Myc Pathway.Cancer medicine · 2025Article
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- EGFRvIII-driven microenvironmental fibroblast activation and transformation accelerate oral cancer progression via lipocalin-2/STAT3 axis.Neoplasia (New York, N.Y.) · 2025Article
- Glioblastoma at the crossroads: current understanding and future therapeutic horizons.Signal transduction and targeted therapy · 2025Review
- CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
- Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.Frontiers in oncology · 2024Review
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- Combining organotypic tissue culture with light-sheet microscopy (OTCxLSFM) to study glioma invasion.EMBO reports · 2023Article
- Combination of Phenethyl Isothiocyanate and Dasatinib Inhibits Hepatocellular Carcinoma Metastatic Potential through FAK/STAT3/Cadherin Signalling and Reduction of VEGF Secretion.Pharmaceutics · 2023Article
- Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the Clinical Treatment of Glioblastoma.Applied biochemistry and biotechnology · 2023Article
- IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.iScience · 2023Article
- Review
- Roles of STAT3 in the pathogenesis and treatment of glioblastoma.Frontiers in cell and developmental biology · 2023Review
- Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?Cancers · 2022Review
- GC-MS/MS Quantification of EGFR Inhibitors,Molecules (Basel, Switzerland) · 2022Article
- Review
- Novel CTRP8-RXFP1-JAK3-STAT3 axis promotes Cdc42-dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells.Molecular oncology · 2022Article
- NF-κB in neurodegenerative diseases: Recent evidence from human genetics.Frontiers in molecular neuroscience · 2022Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Qifan ZhengDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Lei HanDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Yucui DongDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Jing TianDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Wei HuangDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Zhaoyu LiuDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Xiuzhi JiaDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Tao JiangDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Jianning ZhangDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Xia LiDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Chunsheng KangDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Huan RenDepartment of Immunology, Harbin Medical University; Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin, China (Q.-F.Z., Y.-C.D., J.T., W.H., Z.-Y.L., X.-Z.J., H.R.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (T.J.); College of Bioinformatics, Harbin Medical University, Harbin, China (X.L.); Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China (L.H., C.-S.K., J.-N.Z.); Chinese Glioma Cooperative Group (CGCG) (L.H., T.J., C.-S.K.).
Capital Medical University · CNHellenic Cooperative Oncology Group · GRBeijing Tian Tan Hospital · CNThe Neurological Institute · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs a commonly mutated form of the epidermal growth factor receptor, EGFRvIII strongly promotes glioblastoma (GBM) tumor invasion and progression, but the mechanisms underlying this promotion are not fully understood.
methodsThrough gene manipulation, we established EGFRvIII-, wild-type EGFR-, and vector-expressing GBM cells. We used cDNA microarrays, bioinformatics analysis, target-blocking migration and invasion assays, Western blotting, and an orthotopic U87MG GBM model to examine the phenotypic shifts and treatment effects of EGFRvIII expression in vitro and in vivo. Confocal imaging, co-immunoprecipitation, and siRNA assays detected the focal adhesion-associated complex and their relationships to the EGFRvIII/JAK2/STAT3 axis in GBM cells.
resultsThe activation of JAK2/STAT3 signaling is vital for promoting migration and invasion in EGFRvIII-GBM cells. AG490 or WP1066, the JAK2/STAT3 inhibitors, specifically destroyed EGFRvIII/JAK2/STAT3-related focal adhesions and depleted the activation of EGFR/Akt/FAK and JAK2/STAT3 signaling, thereby abolishing the ability of EGFRvIII-expressing GBM cells to migrate and invade. Furthermore, the RNAi silencing of JAK2 in EGFRvIII-expressing GBM cells significantly attenuated their ability to migrate and invade; however, as a result of a potential EGFRvIII-JAK2-STAT3 activation loop, neither EGFR nor STAT3 knockdown yielded the same effects. Moreover, AG490 or JAK2 gene knockdown greatly suppressed tumor invasion and progression in the U87MG-EGFRvIII orthotopic models.
conclusionTaken together, our data demonstrate that JAK2/STAT3 signaling is essential for EGFRvIII-driven migration and invasion by promoting focal adhesion and stabilizing the EGFRvIII/JAK2/STAT3 axis. Targeting JAK2/STAT3 therapy, such as AG490, may have potential clinical implications for the tailored treatment of GBM patients bearing EGFRvIII-positive tumors.
Indexed as
AnimalsAntineoplastic AgentsBrain NeoplasmsCell Line, TumorEnzyme InhibitorsErbB ReceptorsFocal AdhesionsGlioblastomaHumansJanus Kinase 2MiceMice, NudeNeoplasm InvasivenessSignal TransductionSTAT3 Transcription FactorTyrphostinsalpha-cyano-(3,4-dihydroxy)-N-benzylcinnamideAntineoplastic AgentsEnzyme Inhibitorsepidermal growth factor receptor VIIIErbB ReceptorsJanus Kinase 2STAT3 protein, humanSTAT3 Transcription FactorTyrphostinsEGFRvIIIfocal adhesionglioblastomainvasionJAK2/STAT3
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