Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer

// Jung-Yu Kan 1, 2 , Meng-Chi Yen 3 , Jaw-Yuan Wang 1, 2, 4 , Deng-Chyang Wu 5 , Yen-Jung Chiu 1, 2 , Ya-Wen Ho 1 , Po-Lin Kuo 1, 4, 6 1 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 3 Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 6 Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan Correspondence to: Po-Lin Kuo, e-mail: kuopolin@seed.net.tw Keywords: Nucleobindin-2 (NUCB-2), nesfatin-1, colon cancer, EMT, metastasis Received: December 30, 2015      Accepted: April 16, 2016      Published: May 02, 2016 ABSTRACT 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 .