ArticlePloS one2015
Microglia Activate Migration of Glioma Cells through a Pyk2 Intracellular Pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- Accumulation of amyloid beta in human glioblastomas.Clinical and experimental immunology · 2020Trial
- Functional sQTLs regulating PTK2B exon 31 splicing uncover an RNA-dependent modulation of its kinase activity and cellular phenotype.Cell communication and signaling : CCS · 2026Article
- Window of opportunity study measuring defactinib and avutometinib delivery in glioblastomas.Cancer chemotherapy and pharmacology · 2026Article
- Review
- Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute β-amyloid infusion model.Journal of neuroinflammation · 2024Article
- Article
- Pyk2/FAK Signaling Is Upregulated in Recurrent Glioblastoma Tumors in a C57BL/6/GL261 Glioma Implantation Model.International journal of molecular sciences · 2023Article
- The PYK2 inhibitor PF-562271 enhances the effect of temozolomide on tumor growth in a C57Bl/6-Gl261 mouse glioma model.Journal of neuro-oncology · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- The Dynamics of Tumor-Infiltrating Myeloid Cell Activation and the Cytokine Expression Profile in a Glioma Resection Site during the Post-Surgical Period in Mice.Brain sciences · 2022Article
- Macrophage/microglia-derived IL-1β induces glioblastoma growth via the STAT3/NF-κB pathway.Human cell · 2022Article
- Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation.Cancers · 2021Article
- Focal adhesion kinase inhibitors, a heavy punch to cancer.Discover oncology · 2021Review
- RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation.Cancer immunology, immunotherapy : CII · 2021Article
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- Tumor Cell Invasion in Glioblastoma.International journal of molecular sciences · 2020Review
- Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma.International journal of nanomedicine · 2020Article
- Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors.International journal of molecular sciences · 2019Article
- Targeted Delivery of Nanoparticulate Cytochrome C into Glioma Cells Through the Proton-Coupled Folate Transporter.Biomolecules · 2019Article
- Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation.Nature communications · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Glioblastoma is one of the most aggressive and fatal brain cancers due to the highly invasive nature of glioma cells. Microglia infiltrate most glioma tumors and, therefore, make up an important component of the glioma microenvironment. In the tumor environment, microglia release factors that lead to the degradation of the extracellular matrix and stimulate signaling pathways to promote glioma cell invasion. In the present study, we demonstrated that microglia can promote glioma migration through a mechanism independent of extracellular matrix degradation. Using western blot analysis, we found upregulation of proline rich tyrosine kinase 2 (Pyk2) protein phosphorylated at Tyr579/580 in glioma cells treated with microglia conditioned medium. This upregulation occurred in rodent C6 and GL261 as well as in human glioma cell lines with varying levels of invasiveness (U-87MG, A172, and HS683). siRNA knock-down of Pyk2 protein and pharmacological blockade by the Pyk2/focal-adhesion kinase (FAK) inhibitor PF-562,271 reversed the stimulatory effect of microglia on glioma migration in all cell lines. A lower concentration of PF-562,271 that selectively inhibits FAK, but not Pyk2, did not have any effect on glioma cell migration. Moreover, with the use of the CD11b-HSVTK microglia ablation mouse model we demonstrated that elimination of microglia in the implanted tumors (GL261 glioma cells were used for brain implantation) by the local in-tumor administration of Ganciclovir, significantly reduced the phosphorylation of Pyk2 at Tyr579/580 in implanted tumor cells. Taken together, these data indicate that microglial cells activate glioma cell migration/dispersal through the pro-migratory Pyk2 signaling pathway in glioma cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.