Previous study has demonstrated that the PI3K/AKT pathway could modulate the Hedgehog signaling pathway in renal cell carcinoma.18 Our findings indicated that MK2206 treatment blocked Sema3C-induced Gli1 protein expression in HCC cells, suggesting Sema3C could act as a mediator in potentiating AKT signaling activation of the Hedgehog pathway in HCC (Fig. 3h). Here, AKT1 is linked to hereditary clear cell renal cell carcinoma.