ANTAGONISTIC ROLE OF RUNX1 IN THE REGULATION OF KLF4 GENE EXPRESSION IN TNBC CELL LINES AND THEIR CSC SUBPOPULATION

FACUNDO COUTO; SOFIA M SOSA; NATALIA FERNANDEZ; LUCIA ESCOBAR; ANA R RAIMONDI; NATALIA RUBINSTEIN

Mar del Plata

Congreso; Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica.; 2023

Sociedad Argentina de Investigacion Clinica

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Therefore, therapies that target CSC in combination with chemotherapy might prevent tumor recurrence. In TNBC patients, the expression of transcription factor RUNX1 correlates with poor prognosis. We identified that RUNX1 is relevant in tumor aggressiveness in TNBC cell models, for the regulation of oncogenes, cell migration and drug resistance. We recently reported that RUNX1 inhibition enhances drug sensitivity in TNBC-CSC. However, the mechanisms involved are still undefined. On the other hand, the transcription factor KLF4 is required to generate CSCs in TNBC and it has been described as a RUNX1 target gene in other tumors. Our goal was to investigate the regulation of KLF4 by RUNX1 in TNBC cell lines. To consider intratumor heterogeneity we used two cell culture models: attached and forced suspension (mimicking CSC). To inhibit RUNX1 transcriptional activity we used the inhibitor AI-10-104. We found that, when RUNX1 activity is inhibited in attached MDA-MB-231 and -468 cell lines KLF4 mRNA and protein are increased, in a dose- and time-dependent manner (p