Effects of insulin-like growth factor binding protein 5 in breast cancer. Schematic presentations of insulin-like growth factor (IGF)-dependent and IGF-independent effects of insulin-like growth factor binding protein 5 (IGFBP-5) in breast cancer. (a) Main effects of IGFBP-5 dependent on IGF in breast cancer. IGFBP-5 binds IGF and blocks activation of IGF signaling. If IGFBP-5 is degraded by specific proteases, IGF releases and activates cell proliferation. IGF-IR, insulin-like growth factor-I receptor. (b) IGFBP-5 enters cells by specific receptors or other pathways and determines the cell fate with its cellular localization. Left (arrow a): nuclear import of IGFBP-5 – there are two mechanism through which IGFBP-5 enters the nucleus: importin-β(IMPβ)-mediated or diffusion. Right (arrow b): cytoplasmic accumulation of IGFBP-5 by interaction with other proteins, and stimulation of antiapoptotic effects and metastasis.