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Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer
- Source :
- Oncotarget
- Publication Year :
- 2015
-
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.
- Subjects :
- 0301 basic medicine
Male
Colorectal cancer
nesfatin-1
mTORC1
Kaplan-Meier Estimate
AMP-Activated Protein Kinases
Metastasis
0302 clinical medicine
AMP-Activated Protein Kinase Kinases
Cell Movement
Mice, Inbred BALB C
EMT
Cell migration
Nucleobindin 2
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Oncology
colon cancer
030220 oncology & carcinogenesis
Colonic Neoplasms
RNA Interference
Signal transduction
Signal Transduction
Research Paper
Adult
Epithelial-Mesenchymal Transition
Nucleobindin-2 (NUCB-2)
Nerve Tissue Proteins
Mechanistic Target of Rapamycin Complex 1
Protein Serine-Threonine Kinases
03 medical and health sciences
Cell Line, Tumor
medicine
Animals
Humans
Nucleobindins
metastasis
Neoplasm Invasiveness
Epithelial–mesenchymal transition
business.industry
Gene Expression Profiling
Calcium-Binding Proteins
AMPK
Zinc Finger E-box-Binding Homeobox 1
Neoplasms, Experimental
medicine.disease
030104 developmental biology
Cancer research
business
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....b646fc3af1e1036b1eb25c37ddf5844c