N-myc Downstream Regulated Gene 1 (NDRG1) Promotes Metastasis of Human Scirrhous Gastric Cancer Cells through Epithelial Mesenchymal Transition

被引：35
作者：
Ureshino, Hiroki [1 ,6 ]
Murakami, Yuichi [1 ]
Watari, Kosuke [1 ]
Izumi, Hiroto [2 ]
Kawahara, Akihiko [3 ]
Kage, Masayoshi [3 ]
Arao, Tokuzo [4 ]
Nishio, Kazuto [4 ]
Yanagihara, Kazuyoshi [5 ]
Kinoshita, Hisafumi [6 ]
Kuwano, Michihiko [7 ]
Ono, Mayumi [1 ]
机构：
[1] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Pharmaceut Oncol, Fukuoka 812, Japan
[2] Univ Occupat & Environm Hlth, Sch Med, Dept Mol Biol, Kitakyushu, Fukuoka 807, Japan
[3] Kurume Univ Hosp, Dept Diagnost Pathol, Kurume, Fukuoka, Japan
[4] Kinki Univ, Sch Med, Dept Genome Biol, Osaka 589, Japan
[5] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan
[6] Kurume Univ, Sch Med, Dept Surg, Kurume, Fukuoka 830, Japan
[7] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Clin Pharmaceut, Lab Mol Canc Biol, Fukuoka 812, Japan
来源：
PLOS ONE | 2012年 / 7卷 / 07期
关键词：
PANCREATIC-CANCER; STOMACH-CANCER; TUMOR-GROWTH; EXPRESSION; PROGRESSION; SUPPRESSOR; FAMILY; ANGIOGENESIS; MICROARRAY; INHIBITOR;
D O I：
10.1371/journal.pone.0041312
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：13
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