R-spondin3 expression induces stem-like properties in mammary tumor cells

FELCHER, C. M.; TOCCI, J. M.; GARCÍA SOLÁ, M. E.; KORDON, E. C.

Newry, Maine

Seminario; Gordon Research Seminar - Mammary Gland Biology; 2019

GRS

R-spondin 3 (RSPO3) belongs to a family of four secreted proteins that potentiate Wnt signalingpathways, which are essential to the maintenance of normal and cancer stem cells (CSC). Wehave recently identified RSPO3 as a novel key modulator of breast cancer development that maybecome a potential target for treatment of the basal subtype, which lacks efficient therapeuticoptions to date. We showed that RSPO3 is expressed in the basal stem cell-enriched compartmentof normal mouse mammary glands whereas it is absent from committed mature luminal cells.Interestingly, expression profile analysis of 1985 human breast carcinoma samples from TheCancer Genome Atlas (TCGA) Network showed significant higher levels of RSPO3 in the Claudin-low-subtype, which is characterized for showing stem-like features. We have also determined thatRSPO3 knockdown in basal-like mouse mammary tumor cells diminishes TCF-LEF activity (i.e.canonical Wnt signaling pathway), AKT and GSK3b phosphorylation, SOX2 expression,mammosphere formation in vitro as well as tumor growth in vivo. In conclusion, our results suggestthat RSPO3 expression plays a relevant role in the maintenance of the CSC compartment inmammary tumors.