title: Mechanism and biological significance of the overexpression of IFITM3 in gastric cancer.
abstract: Interferon‑induced transmembrane protein 3 (IFITM3) has been recently identified as a potential molecular marker. IFITM3 has been reported to be upregulated in various human diseases, including colon and breast cancer, astrocytoma, as well as ulcerative colitis. However, the clinical significance and underlying mechanisms of IFITM3 dysregulated expression in gastric cancer (GC) remain to be determined. The present study aimed to evaluate the expression of IFITM3 in human gastric tumor cells and specimens and investigate the effects of IFITM3 knockdown in the regulation of GC growth and its potential mechanism. IFITM3 expression was significantly overexpressed in the GC cell lines and GC tissues compared with corresponding normal controls by RT‑qPCR, western blot analysis and immunohistochemistry, and this overexpression was correlated with tumor differentiation, lymph node and distant metastasis, and advanced tumor node metastasis stages. Furthermore, knockdown of IFITM3 expression suppressed tumor cell migration, invasion and proliferation significantly in vitro, arrested tumor cells at the G0/G1 phase and reduced the cell numbers in the S phase of the cell cycle. We preliminarily confirmed that IFITM3 can be mediated by the activities of Wnt/β-catenin signaling. Further investigation revealed that silencing of IFITM3 effectively reversed the epithelial-to-mesenchymal transition (EMT) phenotype and reduced the activities of MMP-2 and MMP-9 expression. Taken together, these data suggested that IFITM3 is a potential therapeutic target for GC.
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qinhao
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jiejing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fei
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Sun
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9