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.
Highlights
Colorectal cancer is the third most common cancer type and the third cause of cancer-related deaths worldwide [1]
In order to further determine whether NUCB-2 overexpression resulted in systematic elevation of NUCB-2, the serum concentration of nesfatin-1, which is derived from N-terminal of NUCB-2, was measured
It suggests that nesfatin-1/ NUCB-2 locally but not systematically regulates signaling pathways of colon cancer cells
Summary
Colorectal cancer ( known colon cancer) is the third most common cancer type and the third cause of cancer-related deaths worldwide [1]. Investigation of novel regulatory pathways of metastasis in colon cancer is beneficial to developing novel therapeutic strategies. High NUCB-2 expression is associated with metastasis and shorter overall survival in clear cell renal cell carcinoma tissue [12]. This evidence suggests that NUCB-2 can induce metastasis in some types of cancer. Nesfatin-1 inhibits cell proliferation in a human adrenocortical carcinoma cell line and an ovarian epithelial carcinoma cell [13, 14]. These controversial results may suggest the regulation of nesfatin-1/NUCB-2 is dependent on tissue specificity
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