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. 2023 Mar 9;31:101633. doi: 10.1016/j.tranon.2023.101633

Fig. 3.

Fig 3

Molecular signaling in angiogenesis. In tip cells, VEGF/VEGFR2 signaling abrogates PTEN and activates AKT which causes nuclear localization of the YAP transcription factor. Nuclear YAP suppresses pro-proliferative signaling. In addition, VEGF signaling suppresses NOTCH expression while upregulating the NOTCH ligand Delta-like 4 (Dll4). The Dll4 activates NOTCH at the surface of stalk cells after which the NICD activates the expression of VEGFR1 while inhibiting VEGFR2 & 3. The decoy receptor VEGFR1 scavenges VEGF which releases PTEN activity and promotes YAP degradation, but part of the YAP is incorporated in adherens junctions and complexed with VE-Cadherin and α-catenin. These actions render stalk cells proliferative.