Furthermore, to elicit the regulation of Notch signaling by Tspan18 is VEGFR2-dependent or not, we knocked down Tspan18 in VEGFR2-deficient cancer cell line Hela and didn't observe significant changes in Notch1, Dll4, EphrinB2 and EphB4 levels (Fig. 7C, Fig. S5C, and data not shown), whereas Notch1 was downregulated when knocking down Tspan18 in VEGFR2-positive cancer cell line 211H (Fig. 7C and Fig. S5C). The gene discussed is DLL4; the disease is cancer.