EGFRvIII uses intrinsic and extrinsic mechanisms to reduce glioma adhesion and increase migration
| Autor: | Jesse K. Placone, Benjamin Yeoman, Frank B. Furnari, Mariam Eick, Pranjali Beri, Afsheen Banisadr, Alison Parisian, Adam J. Engler |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Integrin Extracellular matrix Focal adhesion 03 medical and health sciences Mice 0302 clinical medicine Glioma Cell Line Tumor medicine PTEN Animals Kinase activity 030304 developmental biology 0303 health sciences biology Brain Neoplasms Cell Biology medicine.disease Cell biology ErbB Receptors Crosstalk (biology) Cytokine 030220 oncology & carcinogenesis biology.protein Glioblastoma Signal Transduction Research Article |
| Zdroj: | J Cell Sci |
| ISSN: | 1477-9137 |
| Popis: | A lack of biological markers has limited our ability to identify the invasive cells responsible for glioblastoma multiforme (GBM). To become migratory and invasive, cells must downregulate matrix adhesions, which could be a physical marker of invasive potential. We engineered murine astrocytes with common GBM mutations, e.g. Ink4a (Ink) or PTEN deletion and expressing a constitutively active EGF receptor truncation (EGFRvIII), to elucidate their effect on adhesion. While loss of Ink or PTEN did not affect adhesion, counterparts expressing EGFRvIII were significantly less adhesive. EGFRvIII reduced focal adhesion size and number, and these cells – with more labile adhesions – displayed enhanced migration. Regulation appears to depend not on physical receptor association to integrins but, rather, on the activity of the receptor kinase, resulting in transcriptional integrin repression. Interestingly, EGFRvIII intrinsic signals can be propagated by cytokine crosstalk to cells expressing wild-type EGFR, resulting in reduced adhesion and enhanced migration. These data identify potential intrinsic and extrinsic mechanisms that gliomas use to invade surrounding parenchyma. |
| Databáze: | OpenAIRE |
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