Signaling Determinants of Glioma Cell Invasion

  • Aneta KwiatkowskaEmail author
  • Marc Symons
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)


Tumor cell invasiveness is a critical challenge in the clinical management of glioma patients. In addition, there is accumulating evidence that current therapeutic modalities, including anti-angiogenic therapy and radiotherapy, can enhance glioma invasiveness. Glioma cell invasion is stimulated by both autocrine and paracrine factors that act on a large array of cell surface-bound receptors. Key signaling elements that mediate receptor-initiated signaling in the regulation of glioblastoma invasion are Rho family GTPases, including Rac, RhoA and Cdc42. These GTPases regulate cell morphology and actin dynamics and stimulate cell squeezing through the narrow extracellular spaces that are typical of the brain parenchyma. Transient attachment of cells to the extracellular matrix is also necessary for glioblastoma cell invasion. Interactions with extracellular matrix components are mediated by integrins that initiate diverse intracellular signalling pathways. Key signaling elements stimulated by integrins include PI3K, Akt, mTOR and MAP kinases. In order to detach from the tumor mass, glioma cells secrete proteolytic enzymes that cleave cell surface adhesion molecules, including CD44 and L1. Key proteases produced by glioma cells include uPA, ADAMs and MMPs. Increased understanding of the molecular mechanisms that control glioma cell invasion has led to the identification of molecular targets for therapeutic intervention in this devastating disease.


Glioblastoma Invasion Migration Rho GTPase PI3K Akt Protease 





Brain-enriched hyaluronic acid binding protein


Dentate gyrus


Dedicator of cytokinesis 180


Extracellular matrix


Engulfment and cell motility-1


Grb-2 associated binder-1


GTPase activating protein


Glioblastoma multiforme


Guanine nucleotide dissociation inhibitor


Guanine nucleotide exchange factor


High grade glioma


Low grade glioma


Lysophosphatidic acid




Monocyte chemotactic protein-1


Mammalian homolog of Drosophila diaphanous


Matrix metalloproteinase


Membrane type metalloproteinase 1


Non-neoplastic brain


Neural stem cell


Platelet-derived growth factor receptor


Phosphatidylinositol 3-kinase


PI3K-dependent kinase 1


Pleckstrin homology domain


Phosphatase and tensin homolog deleted on chromosome ten


Crk-associated substrate


Rho-associated coiled-coil forming kinase


Receptor tyrosine kinase


Secreted protein acidic and rich in cystein


Subventricular zone


Tumor associated macrophage


Transforming growth factor-β-1


Tissue inhibitor of metalloproteinases






Vascular endothelial growth factor


Vascular endothelial growth factor receptor-1


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Center for Oncology and Cell Biology, Laboratory for Brain Tumor Biology, Feinstein Institute for Medical ResearchManhassetUSA

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