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Amplification of 8p11-12 in human breast cancers is associated with increased proliferation and tumor grade and reduced metastasis-free patient survival. We identified  Zeppo1  ( zinc finger elbow-related proline domain protein 1 ) ( FLJ14299/ZNF703 ) within this amplicon as a regulator of cell adhesion, migration, and proliferation in mammary epithelial cells. Overexpression of  Zeppo1  reduces cell–cell adhesion and stimulates migration and proliferation. Knockdown of  Zeppo1  induces adhesion and lumen formation. Zeppo1 regulates transcription, complexing with Groucho and repressing  E-cadherin  expression and Wnt and TGFβ reporter expression. Zeppo1 promotes expression of metastasis-associated p120-catenin isoform 1 and alters p120-catenin localization upon cell contact with the extracellular matrix. Significantly,  Zeppo1  overexpression in a mouse breast cancer model increases lung metastases, while reducing  Zeppo1  expression reduces both tumor size and the number of lung metastases. These results indicate that  Zeppo1  is a key regulator of breast cancer progression.

Zeppo1 is a novel metastasis promoter that represses E-cadherin expression and regulates p120-catenin isoform expression and localization