RUNX1 and its understudied role in breast cancer.
The transcription factor Runt-related transcription factor 1 (RUNX1) is critical for the earliest steps of hematopoiesis. RUNX1 was originally identified as a gene fusion in acute myeloid leukemia (AML) and thus has garnered heavy attention as a tumor suppressor in hematopoietic malignancies. However, RUNX1 is also strongly expressed in breast epithelia and may be misregulated during tumorigenesis. Here, I discuss our recent work implicating RUNX1 in proliferation control during breast epithelial-acinar morphogenesis. My goal is to place these findings in the context of a handful of other reports, which together argue that RUNX1 could act as a tumor suppressor gene in breast cancer. Testing this hypothesis requires focused in vivo studies, because the major commercial platform for global mRNA expression profiling does not reliably reflect RUNX1 levels. Our in vitro results indicate that hyperproliferation in RUNX1-deficient breast epithelia relies on another family of transcription factors, the Forkhead box O (FOXO) proteins. FOXOs could, therefore, represent a synthetic-lethal target for RUNX1-deficient tumors if the hypothesized link to breast cancer is correct.
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. kjanes@virginia.edu
Kevin A
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Janes
D061354:Acinar Cells / Q000378:metabolism*; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D050676:Core Binding Factor Alpha 2 Subunit; D051858:Forkhead Transcription Factors; C493728:RUNX1 protein, human