R-spondin3 Is Associated with Basal-Progenitor Behavior in Normal and Tumor Mammary Cells

Autor: Omar A. Coso, Anabella Srebrow, Roberto Meiss, Johanna M. Tocci, Edith C. Kordon, Martín E García Solá, María Victoria Goddio, Natalia Rubinstein, Carla M. Felcher, María Noel Zimberlin, Martín Carlos Abba
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Medicina
Otras Ciencias Biológicas
Mammary gland
Breast Neoplasms
Mammary Neoplasms
Animal
Biology
WNT-signalling
Receptors
G-Protein-Coupled
Ciencias Biológicas
purl.org/becyt/ford/1 [https]
03 medical and health sciences
Basal (phylogenetics)
Mice
Breast cancer
RSPO3
Cell Line
Tumor
medicine
Animals
Humans
Breast
purl.org/becyt/ford/1.6 [https]
Wnt Signaling Pathway
breast-cancer
Progenitor
Cell Proliferation
Cancer
Mammary tumor
Wnt signaling pathway
Core Binding Factor alpha Subunits
Cell Differentiation
Epithelial Cells
medicine.disease
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
Oncology
Cancer research
Female
mammary-gland
R-spondin3 (RSPO3)
Thrombospondins
Mammary cells
CIENCIAS NATURALES Y EXACTAS
Zdroj: SEDICI (UNLP)
Universidad Nacional de La Plata
instacron:UNLP
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Popis: 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.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Databáze: OpenAIRE
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