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![Angiogenesis: the Yin and Yang in intrahepatic cholangiocarcinoma](https://image.oaes.cc/4d90c6ca-44e6-45df-b20b-3654bbb9813d/hr9053.fig.2.jpg)
Figure 2. VEGFR and Tie-2 pathway. On the endothelial cell surface, VEGF binding to its cognate receptor family lead to the activation of a variety of signaling pathway involved in survival (PI3K-AKT), migration (P38/MAPK and FAK/Paxillin), and proliferation (MAPK). Ang-2 is the main competitor of Ang-1 for Tie-2 binding. Under normal conditions, Ang-1 binds Tie-2 to maintain vascular integrity. In pathological conditions, Ang-2 is overexpressed and induces endothelial destabilization, inflammation, and vascular remodeling. Both VEGFR and Tie-2 pathways promote the initiation of new vessel formation and maturation. A hypoxic TME determines an overexpression of VEGF and Ang-2 and induces neoangiogenic processes. The figure was created with Biorender.com.