Dow Lukas E, Humbert Patrick O
Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Center, Melbourne, Australia.
Int Rev Cytol. 2007;262:253-302. doi: 10.1016/S0074-7696(07)62006-3.
A large body of work on Drosophila melanogaster has identified and characterized a number of key polarity regulators, many of which are required for the regulation of multiple other processes including proliferation, migration, invasion, and tumorigenesis. Humans possess either single or multiple homologues of each of the Drosophila polarity proteins, and in most cases, these are highly conserved between species, implying an important and conserved function for each of the polarity complexes. Recent studies in cultured mammalian epithelial cells have shed some light on the requirement for the polarity complexes in the regulation of epithelial cell function, including an unexpected link to the regulation of directed cell migration. However, many questions still remain regarding the molecular mechanisms of polarity regulation and whether disruption of polarity protein function is an important step in the development of human cancers. Here we will review what is currently understood about the regulation of cell polarity, migration, and invasion and the level of functional conservation between Drosophila and mammalian tissues. Particular reference will be made as to how the Scribble and Par polarity complexes may be involved in the regulation of apical-basal polarity, migration, and tumorigenesis.
大量针对黑腹果蝇的研究已经鉴定并表征了许多关键的极性调节因子，其中许多因子对于包括增殖、迁移、侵袭和肿瘤发生在内的多种其他过程的调节是必需的。人类拥有果蝇极性蛋白中每一种的单个或多个同源物，并且在大多数情况下，这些同源物在物种间高度保守，这意味着每个极性复合体都具有重要且保守的功能。最近对培养的哺乳动物上皮细胞的研究揭示了极性复合体在调节上皮细胞功能中的需求，包括与定向细胞迁移调节的意外联系。然而，关于极性调节的分子机制以及极性蛋白功能的破坏是否是人类癌症发展中的重要步骤，仍然存在许多问题。在这里，我们将综述目前对细胞极性、迁移和侵袭调节以及果蝇和哺乳动物组织之间功能保守程度的理解。将特别提及Scribble和Par极性复合体如何可能参与顶-基极性、迁移和肿瘤发生的调节。
