fh535 and Brain-Neoplasms

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.

Topics: Adult; Antineoplastic Agents; Autocrine Communication; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; beta Catenin; Brain Neoplasms; Calcium-Binding Proteins; Carrier Proteins; Cell Line, Tumor; Cell Movement; Cell Proliferation; EGF Family of Proteins; Endothelial Growth Factors; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Glioma; Humans; Kaplan-Meier Estimate; Ligands; Male; Membrane Proteins; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Oncogenes; Protein Binding; Protein Interaction Maps; RNA Interference; Signal Transduction; Sulfonamides; Thyroid Hormone-Binding Proteins; Thyroid Hormones; Time Factors; Transcription Factor 4; Transcription Factors; Transcription, Genetic; Transfection