Figure 1.

The potential mechanisms and pathways associated with IGFBP7 and cancer. IGFBP7 is expressed at both the protein and mRNA levels in most normal tissues, including the brain, liver, pancreas, and skeletal muscle, and is discharged into circulation. Insulin, IGF-1, and IGF-2 can bind to insulin receptors (INSR-A and INSR-B), IGF-2R has binding affinity only for IGF-2. Ligand activation of IGF-1R results in intrinsic tyrosine kinase phosphorylation. Also, it broadly activates (a crescent is placed backward with “backward” effect in the schema) three main (signaling) pathways: IRS-PI3K-AKT-mTOR signaling, Ras-MEK-ERK pathways, and Ras-MAPK signaling. The first two major pathways induce epithelial cells to lose their cell-cell adhesion and acquire the cellular identity of the mesenchymal phenotype. Loss of epithelial markers such as the cell adhesion molecule E-cadherin and the gain of Vimentin and other mesenchymal markers are considered hallmarks in the initiation and execution of EMT. Activation of the three pathways induces many different effects such as protein synthesis, proliferation, anti-apoptosis, cell survival, and growth. EMT: epithelial-mesenchymal transition; IGF: insulin-like growth factor; IGFBP7: IGF binding protein 7; IGF-1R: IGF-1 receptor; IGF-2R: IGF-2 receptor; INSR: insulin receptor; IRS: insulin receptor substrate; MAPK: mitogen-activated protein kinase; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase.