The Six1 gene is a key regulator of embryonic development that requires interaction with the Eya family of proteins (Eya1-4) to activate transcription of genes involved in neurogenesis, myogenesis, and nephrogenesis. Overexpression of Six1 and Eya is observed in a number of cancers. In breast cancer, high levels of Six1 correlate with reduced time to relapse and metastasis and decreased survival only when high levels of Eya2 are also expressed.
In a recent study, Farabaugh and colleagues from the University of Colorado, Aurora, showed that knockdown of Eya2 in MCF7 mammary carcinoma cells reversed the ability of Six1 to induce several pro-metastasis features, including TGF-β signaling and expression of characteristics associated with epithelial-mesenchymal transition (EMT, loss of cell-cell adhesion and an increase in cell mobility) and cancer stem cells. These findings suggest that that Eya2 is a necessary cofactor for the metastasis-promoting activities of Six1 and that targeting these factors may inhibit progression of breast cancer. The investigators noted that “[since] Six1 and Eya2 are not highly expressed in most adult tissues, the Six1-Eya interaction may be a valuable future therapeutic target whose inhibition would be expected to impair breast cancer progression while conferring limited side effects.” ■
Farabaugh SM, et al: Oncogene 31:552–562, 2012.