Elucidation of the molecular mechanisms of early breast cancer invasion and metastasis

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Cancer progression by which epithelial tumor cells acquire a more motile and invasive phenotype has been closely linked to the epithelial-mesenchymal transition (EMT) process. We found that GEP100-Arf6-AMAP1 pathway is important for acquisition of mesenchymal invasive phenotypes of breast cancers and TP53 alterations link to this process. Metabolic pathway regulated by mutant p53 is required for Arf6 activation. The clinical specimens of human breast cancer showed that the expression of GEP100-Arf6-AMAP1 signal correlated with recurrence after radiotherapy. Database analysis also showed that co-incidence of TP53 mutations and the high expression of this signal pathway statistically correlate with poor survival. These results suggest that generation of the Arf6-based mesenchymal invasive pathway by TP53 alterations regulate malignant progression and appears to be crucial for poor prognosis in breast cancer.