Effect Of Ezrin On The EMT Of Metastatic Breast Cancer

EMT(epithelial to mesenchymal transition) is a biological process that epithelial cells transform into mesenchymal phenotype through a specific program. It plays an important role in physiological and pathological processes and is found to be the key step in breast cancer metastatic cascade recently. In a previous study, we have established a novel mouse model using human-derived orthotopic breast tissue and breast cancer cell lines. By comparing the primary cell and parent cell, we found that EMT markers changed. Proteomic analysis found 81 differentially expressed protein between 2-D cultured parent cell and primary cell obtained from implanted normal human breast tissue. Within these protein, ezrin and cortactin were both significantly changed. Knockdown of ezrin could suppress tumor cell migration and invasion in vitro, up-regulate E-cadherin and down-regulateα-SMA. It induced the MET partly by suppress transcription factors snail,slug,twist1,twist2. Ezrin regulated the expression of cortactin but cortactin had no effect on ezrin. Co-immunoprecipitation analysis also showed the direct connection between ezrin and cortactin. Tissue microarray also showed a significant positive association between ezrin and cortactin. These findings indicate that ezrin have a potential function to play a metastasis facilitator by up-regulating cortactin to promote EMT. Ezrin and cortactin may be potential markers in the therapeutic and prognostic of breast cancer.