R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells

R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes, including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell...

Descripción completa

Detalles Bibliográficos
Autores: Tocci, Johanna Melisa, Felcher, Carla María, Garcia Sola, Martin Emilio, Goddio, Maria Victoria, Zimberlin, Maria Noel, Rubinstein, Natalia, Srebrow, Anabella, Coso, Omar Adrian, Abba, Martín Carlos, Meissl, Roberto Jose, Kordon, Edith Claudia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/88986
Acceso en línea:http://hdl.handle.net/11336/88986
Access Level:acceso abierto
Palabra clave:RSPO3
mammary-gland
breast-cancer
WNT-signalling
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes, including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell–enriched compartment of normal mouse mammary glands but is absent from committed mature luminal cells in which exogenous RSPO3 impairs lactogenic differentiation. RSPO3 knockdown in basal-like mouse mammary tumor cells reduced canonical Wnt signaling, epithelial-to-mesenchymal transition-like features, migration capacity, and tumor formation in vivo. Conversely, RSPO3 overexpression, which was associated with some LGR and RUNX factors, highly correlated with the basal-like subtype among patients with breast cancer. Thus, we identified RSPO3 as a novel key modulator of breast cancer development and a potential target for treatment of basal-like breast cancers. Significance: These findings identify RSPO3 as a potential therapetuic target in basal-like breast cancers. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4497/F1.large.jpg.

Similares en LA Referencia