Figure 1.

Proposed model for the angiocrine action of APLN in glioma growth. Endothelial cells produce and release the hormonal peptide apelin (APLN), which operates on GSCs, through its cognate receptor the G protein–coupled receptor APLNR. The APLN/APLNR complex allows the activation of the glycogen synthase kinase, GSK3β (nonphosphorylated on S9) and maintains in turn the stemness properties of GSCs. The competitive antagonist MM54 counteracts the effect of endothelial cells on GSCs and reduces tumor growth in mice. GSCs indicate glioblastoma stem-like cells.