The role of Wnt-induced secreted proteins (WISPs) in gastric cancer

摘要: Introduction: It has been recently shown that the WISP proteins(Wnt-inducted secreted proteins), a group of intra- and extra-cellular regulatory proteins, have implicated in initiation progression variety types tumours including colorectal breast cancer. However, role proteins gastric cancer (GC) cells clinical implication not yet fully elucidated. Materials methods: The expression transcript cohort GC patients was analysed using real-time quantitative PCR immunohistochemistry, respectively. The panel recognised EMT (epithelial-mesenchymal transition) markers were quantified (Q-PCR) paired tumour normal tissues. WISP-2 knockdown sublines anti-WISP-2 ribozyme transgenes created cell lines AGS HGC27. Using models extracted from tissue samples, protein microarray used to search for potential partners signalling pathways involved with WISP-2. Subsequently, biological functions, namely, growth, adhesion, migration invasion, studied. Potential mechanisms related EMT, extracellular matrix MMP (Matrix metalloproteinases) pathways were investigated. Results: Expression frequently detected Levels WISP-2, WISP-1 WISP-3, significantly correlated early TNM staging differentiation status. High levels associated favourable outcome survival patients. We also found inversely Twist Slug samples. Knockdown increased rate proliferation, invasion influenced biomarkers Twist, Ecadherin.Using an antibody based microarray, ERK, JNK as well AKT were found be co-precipiated human proteins. Furthermore, demonstrated change ERK phophorylation. Mechanistically, suppressed metastasis through reversing epithelial-mesenchymal transition suppressing activity MMP-9 MMP-2 via ERK. Cell motility analysis indicated contributed cells’ motility, effect attenuated by PLC-γ small inhibitors. Conclusions: WISP-2 expressions are linked disease profound influence on adhesion is powerful factor reverse process these cells. These effects its involvement pathways, which turn modulate activities. Together, important regulator cellular function It acts suppressor