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

// Seok-Jun Kim 1,8 , Yuan-Guo Wang 2 , Hyun-Woo Lee 1,3 , Hyeok Gu Kang 1,8 , Sun-Hyuk La 1,3 , Il Ju Choi 4 , Tatsuro Irimura 5 , Jae Y. Ro 6 , Robert S. Bresalier 7 and Kyung-Hee Chun 1,8 1 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea. 2 Minimally Invasive Tumor Therapy Laboratory, Radiology Department, Beth Israel Deaconess Medical Center, Boston, MA, USA. 3 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea. 4 Center for Gastric Cancer, Division of Translational & Clinical Research I, National Cancer Center, Gyeonggi-do, Republic of Korea. 5 Institute of medical innovation, St. Luke’s international Hospital, Chuo-ku, Tokyo, Japan. 6 The Methodist Hospital, Department of Pathology and Genomic Medicine, Weil Medical College of Cornell University, Houston, TX, USA. 7 Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 8 Brain Korea 21 PLUS Project for Medical Science, Yonsei University. Correspondence: Kyung-Hee Chun, email: // Keywords : Neogenin-1, Galectin-3, Heat shock factor (HSF)-1, Cancer metastasis, Gastric cancer Received : March 5, 2014 Accepted : May 12, 2014 Published : May 13, 2014 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.