Cell Polarity in Motion: Redefining Mammary Tissue Organization Through EMT and Cell Polarity Transitions
Cell Polarity in Motion: Redefining Mammary Tissue Organization Through EMT and Cell Polarity Transitions
复制标题
DOI：
10.1007/s10911-010-9180-2
复制
发表时间：
2010-06-01
影响因子：
2.5
通讯作者：
Humbert, Patrick O.
中科院分区：
文献类型：
--
作者：
Godde, Nathan J.;Galea, Ryan C.;Humbert, Patrick O.
上皮向间充质转化（EMT）及其通过间充质向上皮转化（MET）的逆转代表上皮可塑性的逐步循环，其允许发育期间的正常组织重塑和多样化。特别是，上皮-间充质可塑性对乳腺发育的许多方面至关重要，并且已被认为是乳腺癌进展的关键过程。这种上皮-间充质可塑性需要复杂的细胞重编程来协调细胞形状的变化，以形成更有利于迁移的替代形态。在此过程中，上皮特征，包括顶端-基底极性和专门的细胞-细胞连接丢失，并获得间充质性质，如与弱细胞-细胞接触相关的前-后极性，增加的运动性，抗凋亡和侵袭性。上皮细胞经历细胞极性状态转换的能力是上皮-间充质可塑性的中心特征。这些细胞极性状态包括一组不同的不对称分布的细胞成分，其被塑造为允许专门的细胞功能，如调节分子的稳态跨越上皮屏障，细胞迁移或细胞多样化通过不对称细胞分裂。每个极性状态都是使用分子工具箱设计的，该工具箱在生物体和细胞类型之间高度保守，可以指导每个不对称性的启动，建立和持续维持。在这里，我们讨论如何EMT途径的目标细胞极性介质，以及如何EMT依赖性的极性状态的变化对乳腺癌的各个阶段的影响。新出现的证据将细胞极性置于增殖和形态控制的界面，因此极性网络内的动态变化在正常乳腺发育和乳腺癌进展中起关键作用。
Epithelial to mesenchymal transition (EMT) and its reversion via mesenchymal to epithelial transition (MET), represent a stepwise cycle of epithelial plasticity that allows for normal tissue remodelling and diversification during development. In particular, epithelial-mesenchymal plasticity is central to many aspects of mammary development and has been proposed to be a key process in breast cancer progression. Such epithelial-mesenchymal plasticity requires complex cellular reprogramming to orchestrate a change in cell shape to an alternate morphology more conducive to migration. During this process, epithelial characteristics, including apical-basal polarity and specialised cell-cell junctions are lost and mesenchymal properties, such as a front-rear polarity associated with weak cell-cell contacts, increased motility, resistance to apoptosis and invasiveness are gained. The ability of epithelial cells to undergo transitions through cell polarity states is a central feature of epithelial-mesenchymal plasticity. These cell polarity states comprise a set of distinct asymmetric distributions of cellular constituents that are fashioned to allow specialized cellular functions, such as the regulated homeostasis of molecules across epithelial barriers, cell migration or cell diversification via asymmetric cell divisions. Each polarity state is engineered using a molecular toolbox that is highly conserved between organisms and cell types which can direct the initiation, establishment and continued maintenance of each asymmetry. Here we discuss how EMT pathways target cell polarity mediators, and how this EMT-dependent change in polarity states impact on the various stages of breast cancer. Emerging evidence places cell polarity at the interface of proliferation and morphology control and as such the changing dynamics within polarity networks play a critical role in normal mammary gland development and breast cancer progression.