EGFRvIII uses intrinsic and extrinsic mechanisms to reduce glioma adhesion and increase migration.

A lack of biological markers has limited our ability to identify the invasive cells responsible for Glioblastoma multiforme. To become migratory and invasive, cells must down regulate matrix adhesions, which could be a physical marker of invasive potential. Murine astrocytes were engineered with common GBM mutations, e.g. Ink4a (Ink) or PTEN deletion and expressing a constitutively active EGF receptor truncation (i.e. 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 dependent not on physical receptor association to integrins but rather on the receptor's kinase activity resulting in transcriptional integrin repression. Interestingly, EGFRvIII intrinsic signals can be propagated by cytokine crosstalk to wildtype EGFR cells, resulting in reduced adhesion and enhanced migration. These data identify potential intrinsic and extrinsic mechanisms that gliomas use to invade surrounding parenchyma