DDR1 signaling is essential to sustain Stat5 function during lactogenesis
DDR1 signaling is essential to sustain Stat5 function during lactogenesis
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DOI：
10.1002/jcb.20618
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Vogel, WF
中科院分区：
文献类型：
--
作者：
Faraci-Orf, E;McFadden, C;Vogel, WF
乳腺的出生后发育是通过内分泌和细胞外基质衍生信号的相互作用实现的。尽管进行了密集的研究，但对这些激素和基底膜刺激的时间和空间协调仍缺乏全面的了解。在这里，我们讨论了胶原蛋白受体DDR1在整合细胞外基质来源的信号和由催乳素受体启动的产乳途径中的作用。我们发现，与对照细胞相比，胶原和催乳素刺激高表达DDR1的乳腺上皮细胞HC11导致更强和更持久的Stat5磷酸化诱导。HC11-DDR1细胞中Stat5活性的增强与β-酪蛋白基因表达的增强相关。相比之下，来自DDR1基因缺失小鼠的细胞在乳源刺激下Stat5活性降低，完全无法诱导β-酪蛋白表达。乳腺组织移植实验证实了在乳汁发生开始之前，DDR1在控制导管分支和肺泡生成方面的细胞自主作用。我们的结果表明，除了激素和细胞因子受体外，DDR1信号转导建立了第三个基质衍生途径，对维持乳腺功能至关重要。
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.