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.
authors: Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.
authors: Hiroki
authors: H
authors: Ureshino
authors: Yuichi
authors: Y
authors: Murakami
authors: Kosuke
authors: K
authors: Watari
authors: Hiroto
authors: H
authors: Izumi
authors: Akihiko
authors: A
authors: Kawahara
authors: Masayoshi
authors: M
authors: Kage
authors: Tokuzo
authors: T
authors: Arao
authors: Kazuto
authors: K
authors: Nishio
authors: Kazuyoshi
authors: K
authors: Yanagihara
authors: Hisafumi
authors: H
authors: Kinoshita
authors: Michihiko
authors: M
authors: Kuwano
authors: Mayumi
authors: M
authors: Ono
mesh_terms: D002293:Adenocarcinoma, Scirrhous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D014746:Vimentin; D000099259:N-myc Downstream-Regulated Gene 1 Protein