Fig. 7

Working model of how the EphA1-activated SDF-1/CXCR4 signaling promotes EPCs’ homing to HCC neovascularization. a In the HCC tumor mass, cEPCs incorporate into the EC layers and tumor vessels (angiogenesis) or migrate to non-vascularized tumor sites to facilitate the initial establishment of the tumorous endothelium, contributing to angiogenesis by providing structural support for nascent vessels (vasculogenesis). b In the tumor microenvironment, ephrinA1/Fc-forced expression of EphA1 activates its downstream signaling molecular AKT and mTOR and then increases the expression and secretion of SDF-1 to the tumor microenvironment. Secreted SDF-1 in turn binds with its receptor CXCR4 on the EPC cell membrane and contributes to the increased angiogenic potency of EPCs and their ability to chemotax to ECs and tumor cells