(A) SIX2 and CDH1 expression values were retrieved from an Oncomine microarray data set (as indicated in the figure) and were plotted by expression value. Statistical analysis was performed using the Pearson’s test.
(B) Model depicting the mechanism by which Six2 represses E-cadherin and promotes metastasis. Overexpression of Six2 in breast cancers leads to increased expression of Zeb2, at least in part through microRNA-mediated regulation. Increased expression of Zeb2 represses E-cadherin transcription by canonical E-box binding and also in part through DNA methylation. Six2 may also promote Cdh1 promoter methylation independent of Zeb2 expression. Decreased expression of E-cadherin by Six2 leads to increased metastasis and decreased survival.