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. 2011 Jun;5(2):111-22.
doi: 10.1007/s12079-011-0130-6. Epub 2011 Apr 26.

Pre- and post-translational regulation of osteopontin in cancer

Pieter H Anborgh  1 , Jennifer C Mutrie, Alan B Tuck, Ann F Chambers
Affiliations

Pre- and post-translational regulation of osteopontin in cancer

Pieter H Anborgh et al. J Cell Commun Signal. 2011 Jun.

Abstract

Osteopontin (OPN) is a matricellular protein that binds to a number of cell surface receptors including integrins and CD44. It is expressed in many tissues and secreted into body fluids including blood, milk and urine. OPN plays important physiological roles in bone remodeling, immune response and inflammation. It is also a tumour-associated protein, and elevated OPN levels are associated with tumour formation, progression and metastasis. Research has revealed a promising role for OPN as a cancer biomarker. OPN is subject to alternative splicing, as well as post-translational modifications such as phosphorylation, glycosylation and proteolytic cleavage. Functional differences have been revealed for different isoforms and post-translational modifications. The pattern of isoform expression and post-translational modification is cell-type specific and may influence the potential role of OPN in malignancy and as a cancer biomarker.

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Figures

Fig. 1
Fig. 1
Schematic of three OPN splice variants, OPN-a, OPN-b and OPN-c, highlighting important functional domains and the differences between isoforms. Full length OPN pre-mRNA is 7 exons in length, with 6 translated exons. Integrin binding (green arrow) occurs at RGD and cryptic SVVYGLR sequences, while CD44 variant receptor binding (blue arrow) occurs near the C-terminus. Thrombin cleavage (T) and MMP cleavage (red zig zag) sites are present in all three isoforms. Serine/threonine phosphorylated residues occur in clusters (circled P) throughout and are modified based on origin and function of OPN. Transglutaminase cross-linking occurs at glutamine residues (Q Q). OPN-b lacks exon 5 and is therefore missing certain phosphorylated sites, while OPN-c lacks exon 4 and is unable to undergo transglutaminase cross-linking. Clinical and functional differences do exist between OPN isoforms, however, these differences appear to be cancer cell type specific
See this image and copyright information in PMC

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