N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition

Hiroki Ureshino, Yuichi Murakami, Kosuke Watari, Hiroto Izumi, Akihiko Kawahara, Masayoshi Kage, Tokuzo Arao, Kazuto Nishio, Kazuyoshi Yanagihara, Hisafumi Kinoshita, Michihiko Kuwano, Mayumi Ono

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.

Original languageEnglish
Article numbere41312
JournalPloS one
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 23 2012

Fingerprint

Epithelial-Mesenchymal Transition
stomach neoplasms
metastasis
Stomach Neoplasms
Genes
Cells
Neoplasm Metastasis
cell lines
Cell Line
Cadherins
Gene Knockdown Techniques
cadherins
genes
snails
Vimentin
vimentin
myc Genes
Peritoneum
peritoneum
Snails

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition. / Ureshino, Hiroki; Murakami, Yuichi; Watari, Kosuke; Izumi, Hiroto; Kawahara, Akihiko; Kage, Masayoshi; Arao, Tokuzo; Nishio, Kazuto; Yanagihara, Kazuyoshi; Kinoshita, Hisafumi; Kuwano, Michihiko; Ono, Mayumi.

In: PloS one, Vol. 7, No. 7, e41312, 23.07.2012.

Research output: Contribution to journalArticle

Ureshino, H, Murakami, Y, Watari, K, Izumi, H, Kawahara, A, Kage, M, Arao, T, Nishio, K, Yanagihara, K, Kinoshita, H, Kuwano, M & Ono, M 2012, 'N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition', PloS one, vol. 7, no. 7, e41312. https://doi.org/10.1371/journal.pone.0041312
Ureshino, Hiroki ; Murakami, Yuichi ; Watari, Kosuke ; Izumi, Hiroto ; Kawahara, Akihiko ; Kage, Masayoshi ; Arao, Tokuzo ; Nishio, Kazuto ; Yanagihara, Kazuyoshi ; Kinoshita, Hisafumi ; Kuwano, Michihiko ; Ono, Mayumi. / N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition. In: PloS one. 2012 ; Vol. 7, No. 7.
@article{cb3eeb14df9140ebbf92bd0017d747ad,
title = "N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition",
abstract = "Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.",
author = "Hiroki Ureshino and Yuichi Murakami and Kosuke Watari and Hiroto Izumi and Akihiko Kawahara and Masayoshi Kage and Tokuzo Arao and Kazuto Nishio and Kazuyoshi Yanagihara and Hisafumi Kinoshita and Michihiko Kuwano and Mayumi Ono",
year = "2012",
month = "7",
day = "23",
doi = "10.1371/journal.pone.0041312",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition

AU - Ureshino, Hiroki

AU - Murakami, Yuichi

AU - Watari, Kosuke

AU - Izumi, Hiroto

AU - Kawahara, Akihiko

AU - Kage, Masayoshi

AU - Arao, Tokuzo

AU - Nishio, Kazuto

AU - Yanagihara, Kazuyoshi

AU - Kinoshita, Hisafumi

AU - Kuwano, Michihiko

AU - Ono, Mayumi

PY - 2012/7/23

Y1 - 2012/7/23

N2 - Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.

AB - Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.

UR - http://www.scopus.com/inward/record.url?scp=84864234370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864234370&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0041312

DO - 10.1371/journal.pone.0041312

M3 - Article

C2 - 22844455

AN - SCOPUS:84864234370

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e41312

ER -