Role of periostin

Periostin, also termed osteoblast-specific factor 2, is a matricellular protein with known functions in osteology, tissue repair, oncology, cardiovascular and respiratory systems, and in various inflammatory settings. However, most of the research to date has been conducted in divergent and circumscribed areas meaning that the overall understanding of this intriguing molecule remains fragmented. Here, we integrate the available evidence on periostin expression, its normal role in development, and whether it plays a similar function during pathologic repair, regeneration, and disease in order to bring together the different research fields in which periostin investigations are ongoing. In spite of the seemingly disparate roles of periostin in health and disease, tissue remodeling as a response to insult/injury is emerging as a common functional denominator of this matricellular molecule. Periostin is transiently upregulated during cell fate changes, either physiologic or pathologic. Combining observations from various conditions, a common pattern of events can be suggested, including periostin localization during development, insult and injury, epithelial–mesenchymal transition, extracellular matrix restructuring, and remodeling. We propose mesenchymal remodeling as an overarching role for the matricellular protein periostin, across physiology and disease. Periostin may be seen as an important structural mediator, balancing appropriate versus inappropriate tissue adaption in response to insult/injury

Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway

Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in metastatic tumors. Periostin expression dramatically enhanced metastatic growth of colon cancer by both preventing stress-induced apoptosis in the cancer cells and augmenting endothelial cell survival to promote angiogenesis. At the molecular level, periostin activated the Akt/PKB signaling pathway through the alpha(v)beta(3) integrins to increase cellular survival. These data demonstrated that the survival-promoting function is crucial for periostin to promote tumor metastasis of colon cancer

Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation

肠道炎症与结直肠癌的发生发展密切相关，溃疡性肠炎（Ulcerative colitis）和克罗恩病(Crohn’s disease)患者发展为结直肠癌的风险明显高于正常人群。因此，研究炎症条件下结直肠癌的发生发展机制有望为预防和治疗肠炎相关结直肠癌提供重要的理论依据。细胞外基质蛋白Periostin与多种疾病的发生发展密切相关。大量的研究表明细胞外基质蛋白Periostin能够影响组织再生、炎症、纤维化以及肿瘤的发生发展。2020年1月21日，我校生命科学学院欧阳高亮教授课题组首次阐明了Periostin蛋白在炎症相关肿瘤发生发展中的功能及其作用机制，并可能为肠炎相关肠癌的治疗提供新的靶点。我校生命科学学院博士生马汉栋为该论文的第一作者，欧阳高亮教授和我校医学院刘迎福副教授为该论文的共同通讯作者。Periostin is a multifunctional extracellular matrix protein involved in various inflammatory diseases and tumor metastasis; however, evidence regarding whether and how periostin actively contributes to inflammation-associated tumorigenesis remains elusive. Here, we demonstrate that periostin deficiency significantly inhibits the occurrence of colorectal cancer in azoxymethane/dextran sulfate sodium-treated mice and in ApcMin/+ mice. Moreover, periostin deficiency attenuates the severity of colitis and reduces the proliferation of tumor cells. Mechanistically, stromal fibroblast-derived periostin activates FAK-Src kinases through integrin-mediated outside-in signaling, which results in the activation of YAP/TAZ and, subsequently, IL-6 expression in tumor cells. Conversely, IL-6 induces periostin expression in fibroblasts by activating STAT3, which ultimately facilitates colorectal tumor development. These findings provide the evidence that periostin promotes colorectal tumorigenesis, and identify periostin- and IL-6-mediated tumor-stroma interaction as a promising target for treating colitis-associated colorectal cancer.We thank Prof. Bin Zhao for providing pCMV5-FLAG-YAP WT and pCMV5-FLAG-YAP 5SA plasmids. We thank Prof. Yongyou Zhang for providing technical support. This work was supported by grants from the National Natural Science Foundation of China (81572598, 81772616, and 81972748), the Natural Science Foundation of Fujian Province of China (2019J02002), and the Health-Education Joint Research Program of Fujian Province (WKJ2016-2-16). 该研究工作获得了国家自然科学基金、福建省自然科学基金等资助

Expression profiles of SnoN in normal and cancerous human tissues support its tumor suppressor role in human cancer.

SnoN is a negative regulator of TGF-β signaling and also an activator of the tumor suppressor p53 in response to cellular stress. Its role in human cancer is complex and controversial with both pro-oncogenic and anti-oncogenic activities reported. To clarify its role in human cancer and provide clinical relevance to its signaling activities, we examined SnoN expression in normal and cancerous human esophageal, ovarian, pancreatic and breast tissues. In normal tissues, SnoN is expressed in both the epithelium and the surrounding stroma at a moderate level and is predominantly cytoplasmic. SnoN levels in all tumor epithelia examined are lower than or similar to that in the matched normal samples, consistent with its anti-tumorigenic activity in epithelial cells. In contrast, SnoN expression in the stroma is highly upregulated in the infiltrating inflammatory cells in high-grade esophageal and ovarian tumor samples, suggesting that SnoN may potentially promote malignant progression through modulating the tumor microenvironment in these tumor types. The overall levels of SnoN expression in these cancer tissues do not correlate with the p53 status. However, in human cancer cell lines with amplification of the snoN gene, a strong correlation between increased SnoN copy number and inactivation of p53 was detected, suggesting that the tumor suppressor SnoN-p53 pathway must be inactivated, either through downregulation of SnoN or inactivation of p53, in order to allow cancer cell to proliferate and survive. These data strongly suggest that SnoN can function as a tumor suppressor at early stages of tumorigenesis in human cancer tissues

Matricellular proteins: multifaceted extracellular regulators in tumor dormancy

National Natural Science Foundation of China [81372841, 31171339, 31071302, J1310027/J0106]; FJNSF [2010J06013

The multifaceted role of periostin in tumorigenesis

Periostin, also called osteoblast-specific factor 2 (OSF-2), is a member of the fasciclin family and a disulfide-linked cell adhesion protein that has been shown to be expressed preferentially in the periosteum and periodontal ligaments, where it acts as a critical regulator of bone and tooth formation and maintenance. Furthermore, periostin plays an important role in cardiac development. Recent clinical evidence has also revealed that periostin is involved in the development of various tumors, such as breast, lung, colon, pancreatic, and ovarian cancers. Periostin interacts with multiple cell-surface receptors, most notably integrins, and signals mainly via the PI3-K/Akt and other pathways to promote cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, aspects related to the function of periostin in tumorigenesis are summarized.National Nature Science Foundation of China [30570935, 30871242]; NCETXMU ; Berkeley Scholar Fellowshi