We thus speculate that in ESCC, MMP-2 is involved in the CCL3–CCR5 axis-derived cell invasion via PI3K/Akt and MEK/ERK pathways, and VEGF-A contributes to angiogenesis via the CCL3–CCR5 axis and PI3K/Akt and MEK/ERK pathways. This evidence concerns the gene AKT1 and esophageal squamous cell carcinoma.