Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer
Authors
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
Neogenin-1 ; Galectin-3 ; Heat shock factor (HSF)-1 ; Cancer metastasis ; 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.