Molecular mechanisms of leptin pro-angiogenic actions in breast cancer could involve two waves, a short-term wave that directly transactivates VEGFR2 in endothelial cells and, a long-term wave inducing the upregulation of MMPs/TIMPs, integrins and NILCO (Notch, IL-1 and leptin crosstalk outcome) in breast cancer cells, which positively regulates VEGF/VEGFR2 expression (Figure 1). The gene discussed is LEP; the disease is breast cancer.