RSPO3 is a glycoprotein secreted by mammary tumor cells that induces Wnt pathway activation and EMT

TOCCI, J. M.; FELCHER, C. M.; GODDIO, M. V.; CASTRO, O. A.; COSO, O. A.; KORDON, E. C.

Rosario

Congreso; 50th Anual Meeting Argentine Society for Biochemistry and Molecular Biology Research; 2014

Argentine Society for Biochemistry and Molecular Biology Research

R-spondins (RSPOs) is a family of secreted proteins that have been implicated in significant processes likeembryonic development, tissue differentiation and human diseases. They have been also postulated as potent stemcell growth factors. In addition, we and other groups have determined that RSPOs are frequently mutated in MouseMammary Tumor Virus (MMTV)-induced tumors, particularly RSPO3. Our results show that mouse and humantumorigenic and non-tumorigenic mammary cells express Rspo3 mRNA, but the levels are higher in basal-like cells.They secrete the protein, which associates with the extracellular matrix and/or the cell membrane, since theirconditioned medium can be enriched by treatment with soluble heparin. Rspo3 treatment of non-tumorigenicmammary epithelial cells induces changes associated to epithelial-mesenchymal transition (EMT). In addition, downregulationof its expression in cultured basal mammary cancer cells causes inhibition of migration, vimentinexpression and repression of the canonical WNT signalling pathway. When transplanted into mice, these RSPO3-KOcells resulted less tumorigenic than control cells. Our results indicate that RSPO3 is a potent oncogene, whichpromotes cancer development through WNT-pathway activation in mammary epithelial cells.