DDR1 signaling is essential to sustain Stat5 function during lactogenesis

被引:34
作者
Faraci-Orf, E [1 ]
McFadden, C [1 ]
Vogel, WF [1 ]
机构
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
关键词
mammary gland; collagen; tyrosine kinase; lactation; prolactin;
D O I
10.1002/jcb.20618
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Postnatal development of the mammary gland is achieved by in interplay of endocrine and extracellular matrix-derived signals. Despite intense research, a comprehensive understanding of the temporal and spatial coordination of these hormonal and basement membrane stimuli is still lacking. Here, we address the role of the collagen-receptor DDR1 in integrating extracellular matrix-derived signaling with the lactogenic pathway initiated by the prolactin receptor. We found that stimulation of DDR1-overexpressing mammary epithelial HC11 cells with collagen and prolactin resulted in stronger and more sustained induction of Stat5 phosphorylation as compared to control cells. Enhanced Stat5 activity in HC11-DDR1 cells correlated with increased beta-casein gene expression. In contrast, cells derived from DDR1-null mice showed reduced Stat5 activation upon lactogenic stimulation and completely failed to induce beta-casein expression. The cell-autonomous role of DDR1 in controlling ductal branching and alveologenesis prior to the onset of lactogenesis was corroborated by mammary tissue transplantation experiments. Our results show that aside from hormone- and cytokine receptors, DDR1 signaling establishes a third matrix-derived pathway vital to maintain mammary gland function.
引用
收藏
页码:109 / 121
页数:13
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