Periostin: biology and function in cancer

Abstract

Periostin (POSTN), a member of the matricellular protein family, is a secreted adhesion-related protein produced in the periosteum and periodontal ligaments. Matricellular proteins are a nonstructural family of extracellular matrix (ECM) proteins that regulate a wide range of biological processes in both normal and pathological conditions. Recent studies have demonstrated the key roles of these ECM proteins in the tumor microenvironment. Furthermore, periostin is an essential regulator of bone and tooth formation and maintenance, as well as cardiac development. Also, periostin interacts with multiple cell-surface receptors, especially integrins, and triggers signals that promote tumor growth. According to recent studies, these signals are implicated in cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, we will summarize the most current data regarding periostin, its structure and isoforms, expressions, functions, and regulation in normal and cancerous tissues. Emphasis is placed on its association with cancer progression, and also future potential for periostin-targeted therapeutic approaches will be explored.

Keywords: Biomarker; Cancer; Metastasis; POSTN; Periostin.

Fig. 1

Periostin gene and protein structures. a Periostin splice variants' structures. In addition to full length, ten other isoforms have been investigated. b Protein domains of periostin and their interactions, The Signal Sequence, the EMI domain, the four FAS-1 domains, and the variable domain and a heparin-binding site (Hbs) that is located at the C-terminal end of the carboxyl-terminal domain (CTD) are all depicted

Fig. 2

Possible roles of periostin in tumorigenesis. Periostin could be involved in the transformation of normal cells into metastatic tumors by preventing apoptosis, and promoting cell proliferation, angiogenesis, migration, EMT, and invasion

Fig. 3

Overview of the signaling pathways involved in periostin-induced metastasis. a Periostin via cross-talk between integrin and EGFR activates the PI3K/Akt signaling pathways and increases MMP-9, vimentin, fibronectin, and N-cadherin. So it affects EMT and increases invasion and metastasis. b Periostin promotes angiogenesis, cell survival, invasion, and metastasis by activating the Akt/PKB signaling pathways. c Periostin activates the ß-catenin dependent pathway by inducing wnt binding to its receptors, resulting in csc self-renewal and metastasis. d The binding of periostin to its receptor activates the NF-ƙB pathway, inducing IL-6 and IL-8 transcription and, ultimately, csc self-renewal and metastasis. e As a result of periostin's interaction with BMP-1, which increased the proteolytic activity of LOX, collagen cross-linking and ECM stiffness are enhanced, resulting in metastasis

Fig. 4

GSCs secrete periostin and activate the αvβ3 integrin signaling pathway, which recruits M2 tumor-associated macrophages from the peripheral blood to the tumor microenvironment. Tumor progression is aided by TAMs (M2)