Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition
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ABSTRACT: The Runx1 transcription factor is essential for hematopoietic differentiation and mutations underlie various leukemias. Here we demonstrate a role for Runx1 in the MCF10 cell series model of breast cancer progression. The highest level of Runx1 that occurs in normal like mammary epithelial cells (MCF10A) is decreased in tumorigenic (MCF10AT1) and metastatic (MCF10CA1a) breast cancer cells. We show that depletion of Runx1 in MCF10A cells results in striking changes in cell morphology and induction of epithelial-mesenchymal transition (EMT) via several signaling pathways. Analyses of breast tumors and patient survival data reveal that loss of Runx1 is associated with poor prognosis and decreased survival. Re-expressing Runx1 in MCF10AT1 breast cancer cells restores the epithelial phenotype. These results identify a novel function for Runx1 in sustaining normal epithelial morphology and preventing EMT. These mechanisms suggest Runx1 levels in early stage tumors can be used as a prognostic indicator of tumor progression.
ORGANISM(S): Homo sapiens
PROVIDER: GSE85857 | GEO | 2017/04/17
SECONDARY ACCESSION(S): PRJNA339558
REPOSITORIES: GEO
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