Fig. 2.

Angiogenesis and angiogenic signaling linking cancer and obesity. In the tumor microenvironment (TME), hypoxia induces pro-angiogenic signals, and the “angiogenic switch”, which in turn supports tumor growth, vascular leakiness, and extracellular matrix (ECM) remodeling. VEGF signaling and ANGPTL4 are important players in these processes and are associated with more aggressive tumor behavior. In obesity, the expansion of the adipose tissue (AT) leads to hypoxia, dysfunctional angiogenesis, inflammation, and elevated expression of VEGF and ANGPTL4. The obese AT secretes angiogenic factors and cytokines that promote tumor progression, including VEGF and ANGPTL4, which also act on the AT itself. Therefore, these two factors are an example of molecules at the crossroad between cancer and obesity, and represent targets for therapeutic intervention in both pathological conditions: inhibition of VEGF signaling and ANGPTL4 can inhibit tumor progression, and improve metabolic conditions in obesity, albeit in the latter the different role of VEGF in early and late disease stages needs to be taken into account