ZNF50 3/ Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

Significance Transcription factor GATA3 has emerged as one of top three altered genes in mammary tumors. In breast cancer, GATA3 expression has been associated with an estrogen receptor (ER)-positive (ER + /luminal) phenotype. ER + tumor cells resemble more differentiated cells, and affected patients are more responsive to therapy and have overall better survival outcomes. Loss of GATA3 correlates with ER − , less differentiated, and more aggressive tumors with poorer prognosis. We have identified zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor that down-regulates GATA3 and promotes aggressive breast cancer. Thus, ZPO2 could be an important oncogenic target for prediction of aggressive breast cancer.