Tumor metastasis with poor prognosis is still the leading cause of deaths among triple-negative breast caner (TNBC) patients. Therefore, understanding the underlying molecular mechanisms of TNBC metastasis and identifying the molecules contributing to the process are of great importance.It would be provided targets for the prevention and treatment of recurrence and metastasis of TNBC.
The expression level of MAP3K1 and its up-or downstream genes,SOX2 and KLF4 were detected using Western blotting assay. Cell migration and proliferation were measure by xCELLigence Real-Time Cell Analyzer (RTCA). Protein interaction was used for co-immunorecipitation.
Compared with metastasis (Met) in TBNC model, the expression of MAP3K1,KLF4,ERK1/2, C-jun and werelower, while SOX2, Ras,Rafand c-Fos were higher in non-metastasis (non-Met) samples. In MAP3K1 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were increased. The expression level of KLF4 was lower than SOX2 reduced or minimal interaction of both. In SOX2 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were decreased, while the expression of KLF4 and MAP3K1 were higher, the interaction of MAP3K1 and KLF4 was inhibited.
It is demonstrated for the very first time that SOX2 and MAP3K1 are playing an important rolesin TNBC cell metastasis by regulating MAPK signaling pathway by interacting with KLF4 .