IGFBP3 (insulin-like growth factor-binding protein 3) is involved in cell survival as well as cell death and tumorigenesis. Epigenetic changes in IGFBP3 affect non-small-cell lung cancer, hepatocellular carcinoma, ovarian cancer, skin cancer, urological cancers, breast cancer and gastric cancer. IGFBP3 is a primary growth inhibitor and can reverse the mitogenic functions of IGF-1 (insulin like growth factor 1) by inducing apoptosis.IGFBP-3 functions both in an IGF-dependent and independent manner. Its IGF-dependent roles involve endocrine function by delivering IGFs to target cells and activating downstream signaling. Meanwhile, its IGF-independent roles include interactions with extracellular matrix and plasma membrane proteins, as well as translocation into the cytoplasm and nucleus. The C-terminal domain has cell-penetrating abilities, enabling the generation of short peptides for intracellular delivery of drugs or genes.
