R-SPONDIN3 EXPRESSION INDUCES STEM-LIKE PROPERTIES IN MAMMARY TUMOR CELLS

CARLA FELCHER; JOHANNA TOCCI; MARTIN GARCIA SOLA; EDITH C. KORDON

Congreso; Gordon Research Conference on Mammary Gland Biology 2019; 2019

R-spondin 3 (RSPO3) belongs to a family of four secreted proteins that poten ate Wnt signaling pathways, which are essen al to the maintenance of normal and cancer stem cells (CSC). We have recently iden ed RSPO3 as a novel key modulator of breast cancer development that may become a poten al target for treatment of the basal subtype, which lacks e cient therapeu c op ons to date. We showed that RSPO3 is expressed in the basal stem cell-enriched compartment of normal mouse mammary glands whereas it is absent from commi ed mature luminal cells. Interes ngly, expression pro le analysis of 1985 human breast carcinoma samples from The Cancer Genome Atlas (TCGA) Network showed signi cant higher levels of RSPO3 in the Claudin- low-subtype, which is characterized for displaying stem-like features. We have also determined that RSPO3 knockdown in basal-like mouse mammary tumor cells diminishes canonical Wnt pathway ac va on, AKT and GSK3ß phosphoryla on, SOX2 expression, mammosphere forma on in vitro as well as tumor growth in vivo. In conclusion, our results suggest that RSPO3 expression plays a relevant role in the maintenance of CSCs in mammary tumors.