MicroRNA Signature of Poorly Resectable Ovarian Cancer

上皮细胞需要正确的极性才能发挥作用。它们的极性和图案是在 器官发生。上皮细胞通常在两个轴上极化，即在根尖-基底外侧轴和在 这种上皮叫做平面细胞极化或PCP。典型的PCP例子包括哺乳动物的特征 皮肤或内脏，如内耳上皮及其感觉性纤毛，以及昆虫的角质结构 无脊椎动物。在果蝇体内建立PCP可作为研究PCP测定和 极化细胞形状的配位一般会发生变化。PCP由远程信号协调，结果 在Frizzled型(FZ)受体及其相关的信号级联(FZ/PCP信号)的激活中起重要作用。这个 FZ/PCP途径在整个进化过程中是保守的，也调节着协调的其他几个方面 细胞极化，包括哺乳动物原肠发育过程中细胞的定向迁移。引人注目的是，FZ/PCP 信号转导通路不同于经典的Wnt/Fz-连环蛋白通路。信号特异性的调控 由相同的受体激活的这两条通路之间的关系还知之甚少，但对 发展和疾病。此外，FZ/PCP信号和由此产生的细胞反应之间的联系， 包括细胞骨架重组和特定的转录事件目前还不清楚。的范围 这一应用是为了研究新发现的PCP测定所需基因的特定作用和 细胞形状变化协调。它们在FZ/PCP信号和/或细胞极化事件中的作用将是 从遗传和生化方面进行了研究。果蝇体内研究与细胞培养的结合 将利用分析和生化实验来实现这些目标。五氯苯酚的生产工艺 建立和WNT/FZ信号与几种医学异常(包括耳聋)有关 内耳上皮)和癌症(该通路的几个组成部分是原癌基因或肿瘤 抑制者)。因此，在本申请中获得的信息将促进我们对细胞的理解 极化和图案化，并将具有医学意义，特别是对癌症发生的研究。

Epithelial cells require correct polarity for their function. Their polarity and patterning is established during organogenesis. Epithelial cells are often polarized in two axes, in the apical-basolateral axis and in the plane of the epithelium, called planar cell polarization or PCP. Typical PCP examples include features of mammalian skin or internal organs, e.g. the inner ear epithelium with its sensory cilia, and insect cuticular structures in invertebrates. The establishment of PCP in Drosophila serves as a paradigm to study PCP determination and the coordination of polarized cell shape changes in general. PCP is coordinated by long range signals, resulting in the activation of the Frizzled (Fz) receptor- and its associated signaling cascade (Fz/PCP signaling). The Fz/PCP pathway is conserved throughout evolution and also regulates several other aspects of coordinated cellular polarization, including directed cell migration during mammalian gastrulation. Strikingly, Fz/PCP ^signaling is distinct from the canonical Wnt/Fz-^Catenin pathway. The regulation of signaling specificity ^between these two pathways activated by the same receptors is only poorly understood, but critical for development and disease. Moreover, the link between Fz/PCP signaling and the resulting cellular responses, including cytoskeletal reorganization and specific transcriptional events are not yet understood. The scope of this application is to investigate the specific roles of newly identified genes required for PCP determination and cell shape change coordination. Their function in Fz/PCP signaling and/or in cellular polarization events will be investigated genetically and biochemically. A combination of in vivo studies in Drosophila, cell culture analyses and biochemical experiments will be utilized to achieve these goals. The processes of PCP establishment and Wnt/Fz signaling have been linked to several medical abnormalities (including deafness in the case of the inner ear epithelium) and cancer (several components of the pathway are proto-oncogenes or tumor suppressors). Thus the information acquired in this application will both advance our understanding of cellular polarization and patterning, and will be of medical relevance, particularly for the study of carcinogenesis.