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.
Keywords:
EMT; Nucleobindin-2 (NUCB-2); colon cancer; metastasis; nesfatin-1.
MeSH terms
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AMP-Activated Protein Kinase Kinases
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AMP-Activated Protein Kinases / genetics*
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AMP-Activated Protein Kinases / metabolism
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Adult
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Animals
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Calcium-Binding Proteins / genetics*
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Calcium-Binding Proteins / metabolism
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Cell Line, Tumor
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Cell Movement / genetics*
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Colonic Neoplasms / genetics*
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Epithelial-Mesenchymal Transition / genetics*
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Gene Expression Profiling / methods
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Gene Expression Regulation, Neoplastic
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Humans
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Kaplan-Meier Estimate
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Male
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Mechanistic Target of Rapamycin Complex 1 / genetics*
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Mechanistic Target of Rapamycin Complex 1 / metabolism
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Mice, Inbred BALB C
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Neoplasm Invasiveness
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Nucleobindins
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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RNA Interference
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Signal Transduction / genetics
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Zinc Finger E-box-Binding Homeobox 1 / genetics*
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Zinc Finger E-box-Binding Homeobox 1 / metabolism
Substances
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Calcium-Binding Proteins
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DNA-Binding Proteins
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NUCB2 protein, human
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Nerve Tissue Proteins
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Nucb1 protein, mouse
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Nucleobindins
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ZEB1 protein, human
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Zinc Finger E-box-Binding Homeobox 1
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Mechanistic Target of Rapamycin Complex 1
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Protein Serine-Threonine Kinases
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STK11 protein, human
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AMP-Activated Protein Kinase Kinases
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AMP-Activated Protein Kinases