The current study corroborate the role of GPER in the complex process of tumor angiogenesis induced by IGF1, supporting the idea that the aberrant cross-talk between receptor tyrosine kinases (RTKs)- and G-protein coupled receptors (GPCR)-mediated signaling may converge on relevant biological responses driven by HIF-1 toward VEGF-dependent new blood vessel formation. This evidence concerns the gene HIF1A and neoplasm.