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首页> 外文期刊>Cell Reports >Aurora A Kinase Regulates Mammary Epithelial Cell Fate by Determining Mitotic Spindle Orientation in a Notch-Dependent Manner
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Aurora A Kinase Regulates Mammary Epithelial Cell Fate by Determining Mitotic Spindle Orientation in a Notch-Dependent Manner

机译：Aurora激酶通过确定有缺口依赖性的方式确定有丝分裂纺锤轴的方向来调节乳腺上皮细胞的命运。

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Cell fate determination in the progeny of mammary epithelial stem/progenitor cells remains poorly understood. Here, we have examined the role of the mitotic kinase Aurora A (AURKA) in regulating the balance between basal and luminal mammary lineages. We find that AURKA is highly expressed in basal stem cells and, to a lesser extent, in luminal progenitors. Wild-type AURKA expression promoted luminal cell fate, but expression of an S155R mutant reduced proliferation, promoted basal fate, and inhibited serial transplantation. The mechanism involved regulation of mitotic spindle orientation by AURKA and the positioning of daughter cells after division. Remarkably, this was NOTCH dependent, as NOTCH inhibitor blocked the effect of wild-type AURKA expression on spindle orientation and instead mimicked the effect of the S155R mutant. These findings directly link AURKA, NOTCH signaling, and mitotic spindle orientation and suggest a mechanism for regulating the balance between luminal and basal lineages in the mammary gland.
机译：乳腺上皮干/祖细胞后代中细胞命运的确定仍然知之甚少。在这里，我们检查了有丝分裂激酶Aurora A（AURKA）在调节基础和管腔乳腺谱系之间的平衡中的作用。我们发现AURKA在基底干细胞中高表达，在较小程度上在腔内祖细胞中表达。野生型AURKA表达促进腔细胞命运，但S155R突变体的表达减少增殖，促进基​​础命运并抑制连续移植。该机制涉及通过AURKA调节有丝分裂纺锤体的方向以及分裂后子细胞的定位。值得注意的是，这是NOTCH依赖性的，因为NOTCH抑制剂阻断了野生型AURKA表达对纺锤体定向的影响，而模仿了S155R突变体的作用。这些发现直接联系了AURKA，NOTCH信号和有丝分裂纺锤体定向，并提出了调节乳腺内腔和基底谱系之间平衡的机制。

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