Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer
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Jung-Yu Kan1,2, Meng-Chi Yen3, Jaw-Yuan Wang1,2,4, Deng-Chyang Wu5, Yen-Jung Chiu1,2, Ya-Wen Ho1, Po-Lin Kuo1,4,6
1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
4Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan
5Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
6Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan
Po-Lin Kuo, e-mail: [email protected]
Keywords: Nucleobindin-2 (NUCB-2), nesfatin-1, colon cancer, EMT, metastasis
Received: December 30, 2015 Accepted: April 16, 2016 Published: May 02, 2016
Recent studies indicate that a high level of nesfatin-1/Nucleobindin-2 (NUCB-2) is associated with poor outcome and promotes cell migration in breast cancer and prostate cancer. However, the role of NUCB2 is not well known in colon cancer. In this study, NUCB-2 level in colon cancer tissue was higher than that in non-tumor tissue. Suppression of NUCB-2 in a colon cancer cell line SW620 inhibited migration and invasion. The microarray analysis showed that low expression level of transcription factor ZEB1 in NUCB-2 knockdowned SW620 cells. In addition, expression level of epithelial-mesenchymal transition (EMT)-related molecules including N-cadherin, E-cadherin, β-catenin, Slug and Twist was affected by NUCB-2 suppression and ZEB1-denepdent pathway. The signaling pathway liver kinase B1(LKB1)/AMP-dependent protein kinase (AMPK)/target of rapamycin complex (TORC) 1 was involved in regulation of NUCB-2-mediated metastasis and EMT properties. Suppression of NUCB-2 inhibited tumor nodules formation in a murine colon tumor model as well. In summary, nesfatin-1/NUCB-2 enhanced migration, invasion and EMT in colon cancer cells through LKB1/AMPK/TORC1/ZEB1 pathways in vitro and in vivo.
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