DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway

DAB2IP (DOC2/DAB2 interactive protein) is downregulated in several cancer types, and its downregulation is involved in tumor cell proliferation, apoptosis, metastasis, and epithelial-mesenchymal transition (EMT). We aimed to investigate the potential role of DAB2IP in the development and progression...

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Main Authors: Liang Sun, Yizhou Yao, Ting Lu, Zengfu Shang, Shenghua Zhan, Weiqiang Shi, Guofeng Pan, Xinguo Zhu, Songbing He
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2018/2968252
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author Liang Sun
Yizhou Yao
Ting Lu
Zengfu Shang
Shenghua Zhan
Weiqiang Shi
Guofeng Pan
Xinguo Zhu
Songbing He
author_facet Liang Sun
Yizhou Yao
Ting Lu
Zengfu Shang
Shenghua Zhan
Weiqiang Shi
Guofeng Pan
Xinguo Zhu
Songbing He
author_sort Liang Sun
collection DOAJ
description DAB2IP (DOC2/DAB2 interactive protein) is downregulated in several cancer types, and its downregulation is involved in tumor cell proliferation, apoptosis, metastasis, and epithelial-mesenchymal transition (EMT). We aimed to investigate the potential role of DAB2IP in the development and progression of gastric cancer. DAB2IP levels were analyzed in human gastric cancer and adjacent normal tissues by Western blots and immunohistochemistry. Potential roles of DAB2IP in regulating gastric cancer cell growth and metastasis were examined by genetic manipulation in vitro. The molecular signaling was determined to understand the mechanisms of observed DAB2IP effects. DAB2IP level is lower in gastric cancer tissues as compared to paired normal tissues. Knockdown of DAB2IP enhanced gastric cancer cell growth and metastasis in vitro and promoted EMT progress at both protein and mRNA levels. Silencing DAB2IP activated extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and the enhanced proliferation and migration ability induced by DAB2IP knockdown were reduced after incubation with U0126 in SGC7901 gastric cancer cells. Inhibition of DAB2IP enhances gastric cancer cell growth and metastasis through targeting the ERK1/2 signaling, indicating that it may serve as a potential target for treatment of gastric cancer.
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institution Kabale University
issn 1687-6121
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language English
publishDate 2018-01-01
publisher Wiley
record_format Article
series Gastroenterology Research and Practice
spelling doaj-art-39bd78082dd3469ba7752b90576ec6932025-02-03T06:42:13ZengWileyGastroenterology Research and Practice1687-61211687-630X2018-01-01201810.1155/2018/29682522968252DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 PathwayLiang Sun0Yizhou Yao1Ting Lu2Zengfu Shang3Shenghua Zhan4Weiqiang Shi5Guofeng Pan6Xinguo Zhu7Songbing He8Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of Radiation Medicine, Medical College of Soochow University, Suzhou 215006, ChinaDepartment of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, ChinaDAB2IP (DOC2/DAB2 interactive protein) is downregulated in several cancer types, and its downregulation is involved in tumor cell proliferation, apoptosis, metastasis, and epithelial-mesenchymal transition (EMT). We aimed to investigate the potential role of DAB2IP in the development and progression of gastric cancer. DAB2IP levels were analyzed in human gastric cancer and adjacent normal tissues by Western blots and immunohistochemistry. Potential roles of DAB2IP in regulating gastric cancer cell growth and metastasis were examined by genetic manipulation in vitro. The molecular signaling was determined to understand the mechanisms of observed DAB2IP effects. DAB2IP level is lower in gastric cancer tissues as compared to paired normal tissues. Knockdown of DAB2IP enhanced gastric cancer cell growth and metastasis in vitro and promoted EMT progress at both protein and mRNA levels. Silencing DAB2IP activated extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and the enhanced proliferation and migration ability induced by DAB2IP knockdown were reduced after incubation with U0126 in SGC7901 gastric cancer cells. Inhibition of DAB2IP enhances gastric cancer cell growth and metastasis through targeting the ERK1/2 signaling, indicating that it may serve as a potential target for treatment of gastric cancer.http://dx.doi.org/10.1155/2018/2968252
spellingShingle Liang Sun
Yizhou Yao
Ting Lu
Zengfu Shang
Shenghua Zhan
Weiqiang Shi
Guofeng Pan
Xinguo Zhu
Songbing He
DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway
Gastroenterology Research and Practice
title DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway
title_full DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway
title_fullStr DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway
title_full_unstemmed DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway
title_short DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway
title_sort dab2ip downregulation enhances the proliferation and metastasis of human gastric cancer cells by derepressing the erk1 2 pathway
url http://dx.doi.org/10.1155/2018/2968252
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