Fig.6. The proposed model for the role of P2Y₂R in pre-metastatic niche formation and tumor metastasis.

Tumor microenvironments such as hypoxia induce ATP release from cancer cells and P2Y₂R expression in monocytes. ATP released from cancer cells can activate P2Y₂R both in monocytes and cancer cells. In monocytes, P2Y₂R activation by ATP induces monocyte recruitment toward the tumor and MMPs secretion, resulting in TAMs formation and enhanced tumor growth. In addition, P2Y₂R activation by ATP induces HIF-1α, resulting in LOX release in cancer cells. Released LOX induces collagen crosslinking, leading to the recruitment of BMDCs and pre-metastatic niche formation.