It was suggested that PI3K → AKT → GSK3β (a downstream substrate of PI3K/Akt pathway) signaling pathway induces the expression of adrenomedullin (AM) through which MCs are recruited to TME, where they recruit endothelial cells by releasing VEGF and FGF-2, induce tissue remodeling by secreting tryptase and MMPs, and consequently promote angiogenesis in RCC [24]. The gene discussed is AKT1; the disease is renal cell carcinoma.