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

Abstract Background 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...

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Main Authors: Linan Zhu, Xudong Zhang, Xiaorui Fu, Zhaoming Li, Zhenchang Sun, Jingjing Wu, Xinhua Wang, Feng Wang, Xiangke Li, Songtao Niu, Mengjie Ding, Zhenzhen Yang, Wanqiu Yang, Meifeng Yin, Lei Zhang, Mingzhi Zhang
Format: Article
Language:English
Published: BMC 2018-01-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12967-018-1383-0
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author Linan Zhu
Xudong Zhang
Xiaorui Fu
Zhaoming Li
Zhenchang Sun
Jingjing Wu
Xinhua Wang
Feng Wang
Xiangke Li
Songtao Niu
Mengjie Ding
Zhenzhen Yang
Wanqiu Yang
Meifeng Yin
Lei Zhang
Mingzhi Zhang
author_facet Linan Zhu
Xudong Zhang
Xiaorui Fu
Zhaoming Li
Zhenchang Sun
Jingjing Wu
Xinhua Wang
Feng Wang
Xiangke Li
Songtao Niu
Mengjie Ding
Zhenzhen Yang
Wanqiu Yang
Meifeng Yin
Lei Zhang
Mingzhi Zhang
author_sort Linan Zhu
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusions These results suggest that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway.
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spelling doaj.art-6f926a2511fd4522b0ee6a5eec6ecbde2022-12-22T01:51:56ZengBMCJournal of Translational Medicine1479-58762018-01-0116111010.1186/s12967-018-1383-0TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathwayLinan Zhu0Xudong Zhang1Xiaorui Fu2Zhaoming Li3Zhenchang Sun4Jingjing Wu5Xinhua Wang6Feng Wang7Xiangke Li8Songtao Niu9Mengjie Ding10Zhenzhen Yang11Wanqiu Yang12Meifeng Yin13Lei Zhang14Mingzhi Zhang15Department of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background 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. Methods 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. Results 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. Conclusions These results suggest that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway.http://link.springer.com/article/10.1186/s12967-018-1383-0Esophageal carcinomaTIPE2ProliferationTumorigenesisWnt/β-catenin pathway
spellingShingle Linan Zhu
Xudong Zhang
Xiaorui Fu
Zhaoming Li
Zhenchang Sun
Jingjing Wu
Xinhua Wang
Feng Wang
Xiangke Li
Songtao Niu
Mengjie Ding
Zhenzhen Yang
Wanqiu Yang
Meifeng Yin
Lei Zhang
Mingzhi Zhang
TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway
Journal of Translational Medicine
Esophageal carcinoma
TIPE2
Proliferation
Tumorigenesis
Wnt/β-catenin pathway
title TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway
title_full TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway
title_fullStr TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway
title_full_unstemmed TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway
title_short TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway
title_sort tipe2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the wnt β catenin pathway
topic Esophageal carcinoma
TIPE2
Proliferation
Tumorigenesis
Wnt/β-catenin pathway
url http://link.springer.com/article/10.1186/s12967-018-1383-0
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