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

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3386-3398
Number of pages13
JournalOncotarget
Volume5
Issue number10
DOIs
StatePublished - 2014

Keywords

  • Cancer metastasis
  • Galectin-3
  • Gastric cancer
  • Heat shock factor (HSF)-1
  • Neogenin-1

ASJC Scopus subject areas

  • Oncology

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