RT Journal Article
SR Electronic
T1 A pleiotropic role for FGF signaling in mammary gland stromal fibroblasts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 565267
DO 10.1101/565267
A1 Zuzana Koledova
A1 Jakub Sumbal
YR 2019
UL http://biorxiv.org/content/early/2019/03/01/565267.abstract
AB Fibroblast growth factor (FGF) signaling is crucial for mammary gland development. While multiple roles for FGF signaling in the epithelium were described, the function of FGF signaling in mammary stroma has not been elucidated. In this study, we investigated FGF signaling in mammary fibroblasts. We found that mammary fibroblasts express FGF receptors 1 and 2 and respond to FGF ligands. In particular, FGF2 and FGF9 induce sustained ERK1/2 signaling and promote fibroblast proliferation and migration in 2D. Intriguingly, only FGF2 induces fibroblast migration in 3D extracellular matrix (ECM) through regulation of actomyosin cytoskeleton and promotes force-mediated collagen remodeling by mammary fibroblasts. Moreover, FGF2 regulates production of ECM proteins by mammary fibroblasts, including collagens, fibronectin, osteopontin, and matrix metalloproteinases. Finally, we show that FGF2 signaling in mammary fibroblasts enhances fibroblast-induced branching of mammary epithelium. Our results demonstrate a pleiotropic role for FGF signaling in mammary fibroblasts with implications for regulation of mammary stromal functions and epithelial branching morphogenesis.Summary statement FGF signaling in mammary fibroblasts regulates fibroblast proliferation, migration, extracellular matrix production and remodeling, and fibroblast-mediated mammary epithelial branching morphogenesis.