IGFBP2 and cancer: Although the precise mechanism of IGFBP-2 oncogenesis in bladder cancer (or other cancers) is unclear, it has a defined role in stimulating angiogenesis and metastasis through IGF1R as described above [40], and its reported oncogenic signaling through integrin-β1 and ERK activation [46] is consistent with the known interaction between activated IGF1R and integrin-β1 with scaffolding by RACK1 and FAK, which promotes proliferative ERK signaling as well as EMT and increased invasiveness [47] (Fig. 2).