Original ArticleEGFL7 is an intercellular EGFR signal messenger that plays an oncogenic role in glioma

- The expression of EGFL7 is associated with tumor grade, pathological type and prognosis for patients with glioma.
- EGFL7 binds with EGFRwt, but not EGFRvIII. EGFL7 activated the downstream pathways of EGFRwt, and enhanced it's oncogenicity.
- EGFR depleted β-catenin/TCF4 complex, promoted EGFL7 transcription, and maintained a continuous EGFL7 autocrine flow line.
- FH535, a β-catenin/TCF4 inhibitor, attenuated oncogenicity of GBM cells by suppressing EGFL7 transcription activity.

Epidermal Growth Factor like domain 7 (EGFL7), also known as Vascular Endothelial-statin (VE-statin), is a secreted angiogenic factor. Recent data have demonstrated the potential oncogenic role and prognostic significance of EGFL7 in several human cancers. However, the clinical signature and further mechanisms of EGFL7's function in gliomagenesis are poorly understood. In the present study, we found that increased EGFL7 expression was associated with tumor grade. High expression of EGFL7 in EGFRvIII-positive glioblastoma multiforme (GBM) was determined to be a strong and independent risk factor for reduced life expectancy. EGFRvIII cells can secrete the EGFL7 protein to improve the activity of the β-catenin/TCF4 Transcription complex in EGFRwt cells, thus promoting their own EGFL7 expression. Our research demonstrates that oncogenic activation of EGFRwt in GBM is likely maintained by a continuous EGFL7 autocrine flow line, and may be an attractive target for therapeutic intervention.