In conclusion, our study for the first time reveals that MMP1 derived from TAMs activates MAPK/Erk signaling pathway through paracrine PAR1 activation, which affects the expression of cell cycle-related gene, including cdc25a/CDK4-cyclin D1 and p21/cdc2-cyclin B1 complexes and ultimately facilitates colon cancer cells proliferation. The gene discussed is CDK4; the disease is malignant colon neoplasm.