The PI3K/AKT signaling pathway controls cell survival, proliferation, metastasis, angiogenesis, and regulates CyclinD1, CyclinB1, MMP1, MMP9, and Ve‐cad in many types of cancer.33, 43, 44, 45, 46, 47 Aberrant activation of this pathway is instrumental in tumorigenesis and tumor progression.48 Our findings demonstrated for the first time that ESC microenvironment suppressed the malignancy of cutaneous melanoma cells due, at least in part, to down‐regulating PI3K/AKT signaling pathway. Here, MMP9 is linked to cutaneous melanoma.