RAP1A and melanoma: Western blot results showed that Rap1A/ Rap1B expression and AKT phosphorylation (thr 308/309) were significantly increased (Fig. 3C–E), and the PI3K inhibitor wortmannin markedly attenuated spheroids under tumor sphere culture conditions (Fig. 3F–G), confirming that PI3K/AKT activation contributes to melanoma stem cell formation.