RUNX1 participation in chemotherapy resistance in TNBC

FERNÁNDEZ, NATALIA BRENDA; CASAIS ONAINDIA, PILAR; SOSA, SOFÍA MARÍA; RUBINSTEIN, NATALIA

Mar del Plata

Congreso; LXIV Reunión Científica Anual Sociedad Argentina de Investigación Clínica; 2019

Triple negative breast cancer (TNBC) is associated with early recurrence and low survival rates. Treatment options are limited due to the lack of specific therapeutic targets and are consequently managed with chemotherapy. This highlights the urgent need for new specific therapeutic targets for this group of patients. TNBC is associated with epithelial-mesenchymal transition (EMT) and enrichment in breast cancer stem cell population. Growing evidences strongly suggest that EMT might be involved in tumor chemoresistance. Our group has shown that RUNX1 could be involved in the aggressiveness of ER-/PR- breast tumor. We reported that RUNX1 is able to promote cell migration and regulate tumor related-gene expression, like RSPO3 and GJA1, in a FOXP3-dependent manner. ChIP assays done in our lab on MDA-MB-231 cell line revealed that RUNX1 has the potential to regulate other transcription factors, such as SOX4, involved in EMT process. Besides we observe a significant up regulation of RUNX1 gene expression in murine tumor cell lines treated with TGFβ. Moreover, RUNX1 has been reported to correlate with poor patient prognosis in human samples of TNBC. Our hypothesis is that RUNX1 promotes EMT in TNBC cells, which make them become chemoresistant while leading metastasis to distant organs. The aim of this study was to investigate RUNX1 participation in the generation of chemotherapy resistance in TNBC. To do this, we use TNBC cell line, doxorubicin (a clinically used drug) and loss of RUNX1 function assays. Here we show that RUNX1 (p=0,0067) and GJA1 (p