| Background&ObjectiveColorectal cancer is the third most common cancer in the world, which has become one of the most common malignant tumors that endangers the health of residents. In spite of the survival rate of patients after surgery is higher than others, but the overall prognosis is not ideal. An important factor which influence the prognosis and survival rate is transfer. So discussion on occurrence mechanism and control factors of Colorectal Cancer Metastasis is important for the treatment of cancer and improve survival rates of patients. The main function of β-catenin is mediating cell adhesion and participating expression of gene. At the cell membrane, E-cadherin-β-catenin complex maintains cell adhesion and prevents the movement of cells. β-catenin at a lower level in cytoplasmic, when it can not be degradated by GSK-3β / APC pathway, p53 / Siah-1 / APC pathway and autophagic lysosomal degradation pathway, β-catenin accumulated into the nucleus. β-catenin can bind TCF and LEF-1, then open a series of tumor-related gene transcription, such as ZEB1, E-cadherin, etc. The tumor necrosis factor receptor associated factor 6(TRAF6) plays a crucial role in NF-κB signaling pathway, MAPK pathway and Src pathway when the three pathways activated by the tumor necrosis faetor(TNF), interleukin-1(IL-1), lipopolysaccharide(LPS) and other inflammatory factors. The three pathways play an important role in the regulation of cell survival, growth, proliferation, differentiation, metastasis, apoptosis, etc and tumor occurrence, development, invasion, the transfer process in osteosarcoma, glioma, lung cancer, stomach cancer and so on. It is reported that TRAF6 promotes proliferation of colorectal cancer cells, but its role in the invasion and metastasis of colorectal cancer is not clear. In this study, we focus on the role of TRAF6 in the colorectal cancer metastasis and its possible regulates mechanism.MethodsWestern Blot tests protein expression; RT-PCR tests m RNA expression; immunohistochemistry and immunofluorescence detect protein expression and localization; knockdown TRAF6 expression using a lentivirus vector-based sh RNA technique; Migration assay, invasion assay, lung metastasis model in nude mice to detect the invasion and metastasis of cells; fluorescent reporter gene to detect β-catenin-mediated Top-Flash activasion.Result1. The levels of TRAF6 m RNA and protein expression are lower in colorectal cancer tissues than in paired normal tissues. In colorectal cancer tissues with lymph node metastasis the levels of TRAF6 protein expression is more higher than in colorectal cancer tissues without lymph node metastasis2. Down-regulation of TRAF6 increased migration and invasive ability of CRC cell in vivo or in vitro.3. Anthropogenic change TRAF6 expression can significantly regulate β-catenin degradation. That is, after up-regulation of TRAF6, the protein level of β-catenin, ZEB1 and β-catenin-mediated transcription activity are decreased; after down-regulation TRAF6, β-catenin protein level increased and emerges the phenomenon of nuclear localization, while ZEB1 protein expression increased. Further research also found that down-regulation β-catenin again while stable interference TRAF6, colorectal cancer cell migration and invasion ability decreased significantly compared to only stable interference TRAF6 in cells.ConclusionsGenerally low expression of TRAF6 presence in human colorectal cancer tissues, and closely associated with lymph node metastasis; knockdown TRAF6 can significantly promote the invasion and metastasis in colorectal cancer cells; knockdown of β-catenin may be reversed after interference TRAF6 promote the migration and invasion in colorectal cancer cells; TRAF6 can suppress metastasis of colorectal cancer by promoting β-catenin degradation. |
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