title: Downregulation of TNFAIP2 suppresses proliferation and metastasis in esophageal squamous cell carcinoma through activation of the Wnt/β-catenin signaling pathway.
abstract: Tumor necrosis factor-α (TNF-α) plays a pivotal role in malignant tumor formation in the tumor microenvironment. To investigate the role of TNF-α in esophageal squamous cell carcinoma (ESCC), we assessed expression profiles of the downstream gene TNF-α-induced protein 2 (TNFAIP2), which e previously unknown in ESCC. TNFAIP2 mRNA and protein expression levels were examined by qRT-PCR and immunohistochemical analysis in 24 fresh and 55 paraffin‑embedded specimens, respectively. The results demonstrated that TNFAIP2 mRNA and protein levels were overexpressed in tumor cells, and TNFAIP2 overexpression was significantly associated with T stage (p=0.049), N stage (p=0.019) and the International Union Against Cancer (UICC) stage (p=0.028). In vitro, TNFAIP2 was highly expressed in TNFα-stimulated Eca109, Kyse150, Kyse510 and TE-10 cells. Lentivirus-mediated RNA interference of TNFAIP2 inhibited cell proliferation, colony formation, migration, invasion and the cell cycle. Moreover, LV-RNAi-mediated TNFAIP2 was found to regulate the Wnt/β-catenin by decreasing expression of some genes downstream from β-catenin (i.e., C-myc, cyclin D1, MMP-7 and Snail), and upregulating expression of E-cadherin and p-GSK-3β. Taken together, these results show that TNFAIP2 may be a potential tumorigenesis gene in ESCC. Our data indicate that TNFAIP2 overexpression may facilitate proliferation and metastasis via activation of the Wnt/β-catenin signaling pathway in ESCC.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D016207:Cytokines; C085839:TNFAIP2 protein, human; D014409:Tumor Necrosis Factor-alpha