RUNX1 participation on TNBC

Sofía María Sosa¹, Natalia Fernández¹, Pilar Casais Onaindia¹, Natalia Rubinstein¹

Triple negative breast cancer (TNBC) is associated with epithelial-mesenchymal transition (EMT), which might be involved in tumor chemoresistance according to growing evidences. Our group has shown that RUNX1 could be involved in the aggressiveness of this subtype of breast tumor. We reported that RUNX1 is able to promote cell migration and regulate tumor gene expression, like RSPO3 and GJA1, EMT and metastasis-related genes. ChIP assays done in our lab revealed that RUNX1 can regulate transcription factors involved in EMT. We observe a significant upregulation of RUNX1 gene expression in TGFβ-treated murine tumor cell lines. Moreover, RUNX1 protein expression correlates with poor patient prognosis in human samples of TNBC. Our aim was to evaluate RUNX1 gene expression and participation in drug-treated TNBC cell lines. Here we show that RUNX1 and GJA1 gene expression is significantly upregulated in doxorubicin-treated MDA-MB-231. Interestingly, we observe that loss of RUNX1 transcriptional activity strongly enhance doxorubicin toxicity in this cell line. Furthermore, we found a potential DNA binding site for glucocorticoid receptor (GR) in RUNX1 gene. MDA-MB-(231, 453 and 468) cell lines show that RUNX1 mRNA is significantly upregulated with dexamethasone (GR agonist) and downregulated with mifepristone (GR antagonist). Therefore, our data suggests that RUNX1 may be involved in TNBC chemoresistance and its expression could be externally regulated by GR activity modulation.