Tissue polarity-dependent control of mammary epithelial homeostasis and cancer development: an epigenetic perspective.
Tissue polarity-dependent control of mammary epithelial homeostasis and cancer development: an epigenetic perspective.
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DOI：
10.1007/s10911-010-9168-y
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发表时间：
2010-03
影响因子：
2.5
通讯作者：
Lelievre, Sophie A.
中科院分区：
文献类型：
--
作者：
Lelievre, Sophie A.
单层上皮的基底顶端组织由基底细胞极处的半桥粒和相对的顶端极处的紧密连接定义，在基底细胞极处细胞与基底膜接触。在乳腺中，紧密连接将细胞与细胞之间的接触密封在管腔中，并将顶侧和基底侧细胞膜分开。这种分离对于组织细胞内信号通路和细胞骨架至关重要。高度组织化的顶极，尤其是顶极极性调节剂（Crb复合物，Par复合物，和Scrib，Dlg，Lgl蛋白）和紧密连接蛋白对细胞表型和基因表达的影响的研究揭示了顶极极性和细胞核之间的复杂关系。这篇综述的目的是强调组织极性轴的顶端在组织表型的表观遗传控制中的作用。顶端极的组织及其在乳腺稳态和肿瘤发生中的重要性将在提出顶端极性蛋白如何间接影响基因表达之前强调，通过影响信号转导和转录调节因子的位置，并直接通过参与染色质相关复合物。顶端极性和细胞核组织之间的关系可能解释顶端极性蛋白如何在顶端改变后从核阻遏物转变为癌行为的核促进剂。顶端极性蛋白对基因表达的表观遗传机制的影响将讨论在乳腺肿瘤的命运顶端极性的支持作用的证据增加。
The basoapical organization of monolayered epithelia is defined by the presence of hemidesmosomes at the basal cellular pole, where the cell makes contacts with the basement membrane, and tight junctions at the opposite apical pole. In the mammary gland, tight junctions seal cell–cell contacts against the lumen and separate the apical and basolateral cell membranes. This separation is critical to organize intracellular signaling pathways and the cytoskeleton. The study of the impact of the highly organized apical pole, and notably apical polarity regulators (Crb complex, Par complex, and Scrib, Dlg, Lgl proteins) and tight junction proteins on cell phenotype and gene expression has revealed an intricate relationship between apical polarity and the cell nucleus. The goal of this review is to highlight the role of the apical pole of the tissue polarity axis in the epigenetic control of tissue phenotype. The organization of the apical pole and its importance in mammary homeostasis and tumorigenesis will be emphasized before presenting how apical polarity proteins impact gene expression indirectly, by influencing signal transduction and the location of transcription regulators, and directly, by participating in chromatin-associated complexes. The relationship between apical polarity and cell nucleus organizations might explain how apical polarity proteins could switch from nuclear repressors to nuclear promoters of cancerous behavior following alterations in the apical pole. The impact of apical polarity proteins on epigenetic mechanisms of gene expression will be discussed in light of increased evidence supporting a role for apical polarity in the fate of breast neoplasms.
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