title: Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seok-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Wang
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Hyeok Gu
authors.initials: HG
authors.lastname: Kang
authors.forename: Sun-Hyuk
authors.initials: SH
authors.lastname: La
authors.forename: Il Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Ro
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bresalier
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D000076249:Heat Shock Transcription Factors; D064593:Heterografts; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D037502:Galectin 3; D000076249:Heat Shock Transcription Factors; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C091279:neogenin