TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway

摘要

Esophageal carcinoma is the eighth prevalent malignancy and ranks the sixth in carcinoma-related death worldwide. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) has been identified as a tumor suppressor in multiple carcinomas. However, its roles and molecular mechanisms underlying esophageal carcinoma progression are still undefined till now. RT-qPCR assay was employed to detect the expression of TIPE2 mRNA. TIPE2 protein expression was measured by using western blot assay. Ad-V and Ad-TIPE2 adenoviruses were constructed to overexpress TIPE2. The effects of TIPE2 overexpression on cell proliferation, invasion and apoptosis were assessed by MTT and Edu incorporation assays, transwell invasion assay and flow cytometry analysis, respectively. The effect of TIPE2 overexpression on xenograft tumor growth was determined by measuring tumor volume and weight, together with immunohistochemistry assay. The effect of TIPE2 overexpression on the Wnt/β-catenin signaling pathway was evaluated by detecting the protein levels of β-catenin, c-Myc and cyclinD1 in EC9076 cells and xenograft tumors of esophageal carcinoma. TIPE2 expression was downregulated in esophageal carcinoma tissues and cells. Adenovirus-mediated TIPE2 overexpression suppressed cell proliferation and invasion, and induced apoptosis in esophageal carcinoma cells. Enforced expression of TIPE2 inhibited tumor growth in vivo, as evidenced by the reduced tumor volume, tumor weight and proliferating cell nuclear antigen expression. Overexpression of TIPE2 inhibited the Wnt/β-catenin signaling pathway in esophageal carcinoma in vitro and in vivo. These results suggest that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway.