The role of osteopontin in the progression of solid organ tumour

a The schematic representation of the location of OPN on human chromosome 4.OPN is at location 4q22.1. Genes encompassed within a 600？kb region on chromosome 4 encodes several noncollagenous bone and dentin proteins including OPN, bone sialoprotein(BSP), dentin matrix protein I (DMPI) and dentin sialophosphoportin (DSPP). All of them are classified as small intergrin-binding ligand N-linked glycoprotein (SIBLING) family proteins. b The signalling pathway of osteopontin. Osteopontin binds integrin α4β1 which causes degradation of phospharylated inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ). Inhibitor of nuclear transcription factor kappa-B (IκBα) and nuclear transcription factor kappa-B (NF-κB; p50 and p65) are both freed following this process. IκBα is degraded by the ubiquitination pathway, while NF-κB enters the cell nucleus where it is phosphorylated and it enhances the expression of pro-survival genes. Moreover, upon binding of osteopontin to integrin α4β1, phosphorylated IKKβ causes inactivation of Forkhead box O3 (FOXO3A). Active FOXO3A is important in decreasing the expression of anti-survival genes such as BIM, BAK and BAX which cause caspase activation and cell apoptosis via mitochondrion and release of cytochrome c. Activation of OPN mediate a diverse range of cellular function, including cell survival/ proliferation, cell-cycle progression, cell migration, endothelial mesenchymal transition, T cell activation, cytokine production, fibrosis, angiogenesis and bone calcification and mineralisation