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

Abstract

Historically associated with the aetiology of human leukaemia, the runtrelated 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.

Global transcriptomic analysis suggests carbon dioxide as an environmental stressor in spaceflight: A systems biology GeneLab case study

“…The key liver genes indicated AEM-dependent reduction in metabolism (ADD1) 30 and unexpectedly, reduced carcinogenesis via inhibition of CTTNB1, which is a major tumorigenic factor. On the other hand, we identified multiple pro-tumorigenic factors, such as NCK1, BCL10, IFNGR1, NCOR2, JAG2, TGFβ1, VLDLR, NFIB, RUNX1 19 , 31 – 33 and CDKN1A/p21 34 , to be linked with AEM housing in skeletal muscle and in mammary gland (Fig. 6 ).…”

RUNX transcription factors: orchestrators of development

“…Since then, point mutations and translocations involving RUNX1 have not only been linked with forms of leukemogenic and hereditary diseases (Sood et al, 2017), but also to epithelial tumors such as skin and oral cancers (Scheitz et al, 2012). RUNX1 is also implicated in the tumorigenesis of hormone-related organs, including breast, ovarian, uterine and prostate cancers (Riggio and Blyth, 2017). Misexpression of RUNX2 is associated with osteosarcoma development (Martin et al, 2011), as well as breast and prostate cancer bone metastasis (Chuang et al, 2017).…”

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer

“…Also in meta-analysis of the gene expression data using curatedOvarianData database, only eight genes of 21 selected genes were significant. Representatively, RUNX1 is reported to be associated with female-related cancers as well as involved in female sex development and a crucial mediator of female hormone signaling [ 26 ]. CCN4 is aberrantly expressed in numerous cancer including ovarian cancer [ 27 ], and its transcript levels are lower in node-positive high-grade tumors and in patients with poor clinical outcome for breast cancer [ 28 ].…”