Figure 1.

The EGFRvIII–OSMR heterodimer activates STAT3, initiating feed-forward expression of OSMR. EGFRvIII (blue) and OSMR (red) interact at the cell surface, leading to STAT3 (green) phosphorylation and phospho-STAT3 translocation to the nucleus. Nuclear phospho-STAT3 binds to the Osmr promoter and increases Osmr transcription. This results in feed-forward signaling through the EGFRvIII–OSMR heterodimer, which significantly increases HGG growth. Additional aspects of this model that could be explored in future are indicated by dashed lines. These include uncovering the role of JAK family kinases in activating STAT3 and determining whether phospho-STAT3 has a role in maintaining EGFRvIII expression. Yellow circles denote phospho-tyrosine.