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Learn MoreTo define transcriptional dependencies of TNBCs, we identified transcription factors highly and specifically expressed in primary TNBCs and tested their requirement for cell growth in a panel of breast cancer cell lines. We found that EN1 is overexpressed in TNBCs and its downregulation preferentially and significantly reduces cellular viability and tumorigenicity in TNBC cell lines. Based on RNA-seq and ChIPseq we found that EN1 regulates genes involved in angiogenesis, neurogenesis, and axon guidance in breast cancer cells. Higher expression of EN1 correlates with shorter overall survival among TNBC patients and with higher risk of developing brain metastases. Thus, EN1 is a prognostic marker and a therapeutic target in this particularly lethal subset of TNBCs. SOURCE: Kornelia Polyak (kornelia_polyak@dfci.harvard.edu) - Polyak Dana-Farber Cancer Institute
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