Abstract
Matricellular proteins differ from other classical extracellular matrix proteins; for instance, they are transiently expressed as soluble proteins rather than being constitutively expressed in pathological conditions, such as acute viral infections. Accumulating studies have revealed that matricellular proteins, including osteopontin and tenascin-C, both of which interact with integrin heterodimers, are involved in inflammatory diseases, autoimmune disorders, and cancers. The concentrations of these matricellular proteins are elevated in the plasma of patients with certain types of cancers, indicating that they play important roles in oncogenesis. Chronic viral infections are associated with certain cancers, which are distinct from non-viral cancers. Viral oncogenes play critical roles in the development and progression of such cancers. It is vital to investigate the mechanisms of tumorigenesis and, particularly, the mechanism by which viral proteins induce tumor progression. Viral proteins have been shown to influence not only the viral-infected cancer cells, but also the stromal cells and matricellular proteins that constitute the extracellular matrix that surrounds tumor tissues. In this review, we summarize the recent progress on the involvement of matricellular proteins in oncogenic virus-induced cancers to elucidate the mechanism of oncogenesis and consider the possible role of matricellular proteins as therapeutic targets in virus-induced cancers.
Highlights
Matricellular proteins exhibit different phenotypes to those of the classical extracellular matrix (ECM) proteins in vivo; for instance, they induce cell motility rather than providing scaffolds for stable cell adhesion [1]
The matricellular proteins are well evidenced to be involved in the tumorigenesis of such cancers, depending on the cell type, and on the expression of viral oncogenes and their associated molecules in the cancer cells
Based on this review of the recent reports, it seems that the potential involvement of the matricellular proteins in viral tumorigenesis has not been fully investigated
Summary
Matricellular proteins exhibit different phenotypes to those of the classical extracellular matrix (ECM) proteins in vivo; for instance, they induce cell motility rather than providing scaffolds for stable cell adhesion [1]. An altered expression of the matricellular proteins has been detected in patients with cancers, suggesting the involvement of these molecules in tumorigenesis It is well-known that chronic virus infections frequently cause tumors. POSTN is known to activate the canonical wingless-related integration site (Wnt) signaling pathways, which are involved in cancer stem cell maintenance [43] Related to this role in the regulation of Wnt signaling, POSTN has been identified as an epithelial-mesenchymal transition (EMT) marker [44]. These two independent interaction-induced signaling pathways are important for the development and maintenance of cancer cells [40].
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