Role of periostin and its antagonist PNDA-3 in gastric cancer metastasis

The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5.Periostin participates in normal physiological activities such as cardiac development,but is also involved in pathophysiological processes in vascular diseases,wound repair,bone formation,and tumor development.It is of increasing interest in tumor biologybecause it is frequently overexpressed in a variety of epithelial carcinomas and is functionally involved in multiple steps of metastasis progression.These include the maintenance of stemness,niche formation,EMT,the survival of tumor cells,and angiogenesis,all of which are indispensable for gastric cancer metastasis.Periostin has been reported to activate the PI-3K/AKT,Wnt,and FAK-mediated signaling pathways to promote metastasis.Therefore,periostin represents a potentially promising candidate for the inhibition of metastasis.In this review article,we summarize recent advances in knowledge concerning periostin,its antagonist PNDA-3,and their influence on such key processes in cancer metastasis as maintenance of stemness,niche formation,epithelialto-mesenchymal transition,tumor cell survival,and angiogenesis.In particular,we focus our attention on the role of periostin in gastric cancer metastasis,speculate as to the usefulness of periostin as a therapeutic and diagnostic target for gastric cancer metastasis,and consider potential avenues for future research.