Oncotarget

Research Papers:

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 and Kyung-Hee Chun _

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Oncotarget. 2014; 5:3386-3398. https://doi.org/10.18632/oncotarget.1960

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Abstract

Seok-Jun Kim1,8, Yuan-Guo Wang2, Hyun-Woo Lee1,3, Hyeok Gu Kang1,8, Sun-Hyuk La1,3, Il Ju Choi4 , Tatsuro Irimura5, Jae Y. Ro6, Robert S. Bresalier7 and Kyung-Hee Chun1,8

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.


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