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Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer

 Seok-Jun Kim  ;  Yuan-Guo Wang  ;  Hyun-Woo Lee  ;  Hyeok Gu Kang  ;  Sun-Hyuk La  ;  Il Ju Choi  ;  Tatsuro Irimura  ;  Jae Y. Ro  ;  Robert S. Bresalier  ;  Kyung-Hee Chun 
 ONCOTARGET , Vol.5(10) : 3386-3398, 2014 
Journal Title
Issue Date
Adenocarcinoma/metabolism* ; Adenocarcinoma/pathology* ; Animals ; Blotting, Western ; Cell Line, Tumor ; Cell Movement*/physiology ; Cell Proliferation*/physiology ; DNA-Binding Proteins/metabolism ; Galectin 3/metabolism ; Gene Expression Regulation, Neoplastic ; Heat Shock Transcription Factors ; Heterografts ; Humans ; Immunoprecipitation ; Membrane Proteins/biosynthesis* ; Mice ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms/metabolism* ; Stomach Neoplasms/pathology* ; Tissue Array Analysis ; Transcription Factors/metabolism ; Transfection ; Up-Regulation
Neogenin-1 ; Galectin-3 ; Heat shock factor (HSF)-1 ; Cancer metastasis ; Gastric cancer
Although elevated expression of neogenin-1 has been detected in human gastric cancer tissue, its role in gastric tumorigenesis remains unclear due to the lack of neogenin-1 studies in cancer. Therefore, we demonstrated here the function and regulatory mechanism of neogenin-1 in gastric cancer. Neogenin-1 ablation decreased proliferation and migration of gastric cancer cells, whereas its over-expression reversed these effects. Xenografted analyses using gastric cancer cells displayed statistically significant inhibition of tumor growth by neogenin-1 depletion. Interestingly, galectin-3 interacted with HSF-1 directly, which facilitated nuclear-localization and binding on neogenin-1 promoter to drive its transcription and gastric cancer cell motility. The galectin-3-increased gastric cancer cell motility was down-regulated by HSF-1 depletion. Moreover, the parallel expression patterns of galectin-3 and neogenin-1, as well as those of HSF-1 and neogenin-1, were detected in the malignant tissues of gastric cancer patients. Taken together, high-expression of neogenin-1 promotes gastric cancer proliferation and motility and its expression is regulated by HSF-1 and galectin-3 interaction. In addition, we propose further studies for neogenin-1 and its associated pathways to provide them as a proper target for gastric cancer therapy.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seok Jun(김석준)
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
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