Analysis of RUNX-CBFβ as a relevant regulator of RSPO3 expression in breast cancer cells

FELCHER, C. M.; ARCUSCHIN, C. D.; STEDILE, M. N.; TOCCI, J. M.; SCHOR, I. E.; BUSHWELLER, J. H.; CASTILLA, L. H.; KORDON, E. C.

Buenos Aires

Simposio; Buenos Aires-Breast Cancer Symposium BA-BCS 2021; 2021

BA-BCS 2021

We have recently determined that R-spondin3 (RSPO3),a secreted protein that potentiates Wnt signaling pathway, isa key modulator of tumor progression and stem cell behavior in basal breast cancer. Previous reports suggested thepotential involvement of the RUNX-CBFβ axis on RSPO3expression in mammary tumor cells. These preliminaryobservations were confirmed by our results showing thatsmall molecules able to inhibit CBFβ-RUNX interactioncaused reduction of RSPO3 mRNA and protein levels inMDA-MB231 breast cancer cells. These treatments alsoinduced inhibition of cell migration, ability that was recoveredupon addition of recombinant RSPO3. To further explore themechanisms underlying the control exerted by RUNX-CBFβon RSPO3, we performed an in silico analysis of publiclyavailable data from two RUNX1 CHIP-seq reports and anATAC-seq study from human breast cell lines. We alignedthe emerging data with the occurrences of the RUNX1DNA-recognition-motif in the Rspo3 locus. This approachrevealed a few putative RUNX1 binding sites. Among them,an intronic Rspo3 region that seems to be particularly activein triple negative (TN) breast cancer cells deserves specialattention. In summary, our results show that RUNX-CBFβtranscriptional activity might affect TN mammary tumors bycontrolling RSPO3 expression levels. More experiments arebeing carried out to determine the mechanisms involved andthe impact of this pathway on TN breast cancer behavior.