KDR and neoplasm: Multiple signaling pathways have been shown to be involved in the regulation of tumor angiogenesis, among which PI3K/Akt signaling is the most important.159 PI3K forms a complex with E-cadherin, β-catenin, and VEGFR-2 and is involved in endothelial signaling mediated by VEGF through the activation of the PI3K/Akt pathway.160 The PI3K/Akt signaling pathway also promotes TNF-induced endothelial cell migration and regulates tumor angiogenesis.161 Matrix metalloproteinases (MMPs) and cyclooxygenase 2 (COX-2) also affect tumor angiogenesis.