SPP1 and breast cancer: Furthermore, in human breast cancer cell lines, OPN has been shown to activate Brk/NF-κB/ATF-4 pathways, the cross-talk of which stimulates VEGF to enhance NRP-1–mediated tumor cell motility and vascular endothelial cell growth factor receptor KDR engagement as a bridging point between epithelial and endothelial cells (146).