Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer

Di Feng,1 Xiaoyu Yu,1 Xing Tian,2 Hongxue Meng,1 Yang Jiang,1 HongTao Song,1 WenQi Li,1 HaoCheng Zhang,3 Jingshu Geng1 1Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, People’s Republic of China; 2Department of Microbiology and Center of Inf...

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Main Authors: Feng D, Yu X, Tian X, Meng H, Jiang Y, Song H, Li W, Zhang H, Geng J
Format: Article
Language:English
Published: Dove Medical Press 2019-10-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/metadherin-promotes-malignant-phenotypes-and-induces-beta-catenin-nucl-peer-reviewed-article-CMAR
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author Feng D
Yu X
Tian X
Meng H
Jiang Y
Song H
Li W
Zhang H
Geng J
author_facet Feng D
Yu X
Tian X
Meng H
Jiang Y
Song H
Li W
Zhang H
Geng J
author_sort Feng D
collection DOAJ
description Di Feng,1 Xiaoyu Yu,1 Xing Tian,2 Hongxue Meng,1 Yang Jiang,1 HongTao Song,1 WenQi Li,1 HaoCheng Zhang,3 Jingshu Geng1 1Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, People’s Republic of China; 2Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150070, People’s Republic of ChinaCorrespondence: Jingshu GengDepartment of Pathology, Harbin Medical University Cancer Hospital, 7th Floor, Outpatient Building, Harbin, Heilongjiang 150081, People’s Republic of ChinaEmail gengjingshu@yeah.netPurpose: Metadherin (MTDH), as an oncogene, is associated with metastasis and poor prognosis. This study investigated MTDH expressions and development of gastric cancer (GC) cell phenotypes and the contribution of MTDH to epithelial–mesenchymal transition (EMT).Patients and methods: MTDH expression was assayed in human GC cell lines and tumor tissue from 92 GC patients. Functional experiments were performed to characterize MTDH activity. Expressions of EMT-related proteins (vimentin and E-cadherin), phosphorylated β-catenin and β-catenin were assayed by immunohistochemistry, Western blotting, immunofluorescence, and co-immunoprecipitation, respectively.Results: MTDH expressions were higher in GC tissue than that in gastric mucosa from the same patient. MTDH overexpression was correlated with metastasis and enhanced malignant GC phenotypes, i.e., proliferation, migration, invasiveness, and chemoresistance. MTDH overexpression was associated with expressions of vimentin, E-cadherin and cancer stem-cell biomarkers including CD44, CD133, and Oct4. MTDH complexed with β-catenin and decreased phosphorylated β-catenin levels to facilitate β-catenin translocation into the nucleus and expressions of downstream genes.Conclusion: MTDH overexpression in GC cells is associated with EMT and development of cancer stem cell malignant phenotypes and affects the subcellular translocation of β-catenin. The results warrant investigation of the prognostic value of MTDH in GC and as a therapeutic target.Keywords: metadherin, gastric cancer, CD44, β-catenin, cancer stem cells
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spelling doaj.art-2f0db8e193914ef2878cf3898abfad572022-12-22T00:48:47ZengDove Medical PressCancer Management and Research1179-13222019-10-01Volume 118911892149079Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric CancerFeng DYu XTian XMeng HJiang YSong HLi WZhang HGeng JDi Feng,1 Xiaoyu Yu,1 Xing Tian,2 Hongxue Meng,1 Yang Jiang,1 HongTao Song,1 WenQi Li,1 HaoCheng Zhang,3 Jingshu Geng1 1Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, People’s Republic of China; 2Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150070, People’s Republic of ChinaCorrespondence: Jingshu GengDepartment of Pathology, Harbin Medical University Cancer Hospital, 7th Floor, Outpatient Building, Harbin, Heilongjiang 150081, People’s Republic of ChinaEmail gengjingshu@yeah.netPurpose: Metadherin (MTDH), as an oncogene, is associated with metastasis and poor prognosis. This study investigated MTDH expressions and development of gastric cancer (GC) cell phenotypes and the contribution of MTDH to epithelial–mesenchymal transition (EMT).Patients and methods: MTDH expression was assayed in human GC cell lines and tumor tissue from 92 GC patients. Functional experiments were performed to characterize MTDH activity. Expressions of EMT-related proteins (vimentin and E-cadherin), phosphorylated β-catenin and β-catenin were assayed by immunohistochemistry, Western blotting, immunofluorescence, and co-immunoprecipitation, respectively.Results: MTDH expressions were higher in GC tissue than that in gastric mucosa from the same patient. MTDH overexpression was correlated with metastasis and enhanced malignant GC phenotypes, i.e., proliferation, migration, invasiveness, and chemoresistance. MTDH overexpression was associated with expressions of vimentin, E-cadherin and cancer stem-cell biomarkers including CD44, CD133, and Oct4. MTDH complexed with β-catenin and decreased phosphorylated β-catenin levels to facilitate β-catenin translocation into the nucleus and expressions of downstream genes.Conclusion: MTDH overexpression in GC cells is associated with EMT and development of cancer stem cell malignant phenotypes and affects the subcellular translocation of β-catenin. The results warrant investigation of the prognostic value of MTDH in GC and as a therapeutic target.Keywords: metadherin, gastric cancer, CD44, β-catenin, cancer stem cellshttps://www.dovepress.com/metadherin-promotes-malignant-phenotypes-and-induces-beta-catenin-nucl-peer-reviewed-article-CMARmetadheringastric cancerCD44β-catenincancer stem cells
spellingShingle Feng D
Yu X
Tian X
Meng H
Jiang Y
Song H
Li W
Zhang H
Geng J
Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer
Cancer Management and Research
metadherin
gastric cancer
CD44
β-catenin
cancer stem cells
title Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer
title_full Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer
title_fullStr Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer
title_full_unstemmed Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer
title_short Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial–Mesenchymal Transition In Gastric Cancer
title_sort metadherin promotes malignant phenotypes and induces beta catenin nuclear translocation and epithelial ndash mesenchymal transition in gastric cancer
topic metadherin
gastric cancer
CD44
β-catenin
cancer stem cells
url https://www.dovepress.com/metadherin-promotes-malignant-phenotypes-and-induces-beta-catenin-nucl-peer-reviewed-article-CMAR
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