| Objective:Breast cancer is the most prevalent cancer in women worldwide and metastatic breast cancer has very poor prognosis. Inflammation has been implicated in migration and metastasis of breast cancer, although the exact molecular mechanism remains elusive. This study aimed to observe the changes in the expression levels of MTDH and the following phenotypes caused by induction of a pro-inflammatory endotoxin.Methods:Differences in the expression levels of MTDH and TLR4, both mRNA and protein levels, were detected by Realtime PCR and Western blot assay. Efficient knockdown of MTDH in MDA-MB-231cell line was achieved by shRNA plasmid construction. The ability of migration and invasion of breast cancer cells were measured by in vitro scratch assay and transwell invasion assay. Endotoxin was added to the culture medium for indicated times and concentrations to induce the inflammatory reaction.Results:we show that the pro-inflammatory endotoxin Lipopolysaccharide (LPS) upregulates the expression of Metadherin (MTDH), a recently identified oncogene, in a number of breast cancer lines. Stable knockdown of MTDH by shRNA in human breast MDA-MB-231cells abolishes LPS-induced cell migration and invasion as determined by several in vitro assays. In addition, knockdown of MTDH diminishes Nuclear Factor-kappa B (NF-κB) activation by LPS and inhibited LPS-induced IL-8and MMP-9production.Conclusions:These results strongly suggest that MTDH is a pivotal molecule in inflammation-mediated tumor metastasis. Since NF-κB, IL-8and MMP-9play roles in LPS-induced invasion or metastasis, the mechanism of MTDH-promoted invasion and metastasis may be through the activation of NF-κB, IL-8and MMP-9, also suggesting a role of MTDH in regulating both inflammatory responses and inflammation-associated tumor invasion. These findings indicate that MTDH involves in inflammation-induced tumor progression, and support MTDH targeting therapy may hold promising prospects in treating breast cancer. |
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