The enigmatic role of RUNX1 in female‐related cancers – current knowledge & future perspectives

Historically associated with the aetiology of human leukaemia, the runt-related transcription factor 1 (RUNX1) gene has in recent years reared its head in an assortment of epithelial cancers. This review discusses the state-of-the-art knowledge of the enigmatic role played by RUNX1 in female-related cancers of the breast, the uterus and the ovary. The weight of evidence accumulated so far is indicative of a very context-dependent role, as either an oncogene or a tumour suppressor. This is corroborated by high-throughput sequencing endeavours which report different genetic alterations affecting the gene, including amplification, deep deletion and mutations. Herein, we attempt to dissect that contextual role by firstly giving an overview of what is currently known about RUNX1 function in these specific tumour types, and secondly by delving into connections between this transcription factor and the physiology of these female tissues. In doing so, RUNX1 emerges not only as a gene involved in female sex development but also as a crucial mediator of female hormone signalling. In view of RUNX1 now being listed as a driver gene, we believe that greater knowledge of the mechanisms underlying its functional dualism in epithelial cancers is worthy of further investigation.