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MicroRNA Signature of Poorly Resectable Ovarian Cancer

难以切除的卵巢癌的 MicroRNA 特征

基本信息

批准号：
8380122
负责人：
CHARLES DRESCHER
金额：
$ 21.1万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8380122
关键词：
Address Apical Biochemical Blood Blood Circulation Blood Tests Cell Culture Techniques Cell Shape Cells Characteristics Cilia Cytoskeletal Modeling Data Detection Development Disease Drosophila genus Epithelial Cells Epithelial ovarian cancer Epithelium Event Evolution Excision Foundations Genes Goals Individual Insecta Invertebrates Knowledge Labyrinth Lead Link Malignant Neoplasms Malignant neoplasm of ovary Measurable Measures Medical Methodology Methods MicroRNAs Microfluidics Molecular Profiling Neoadjuvant Therapy Nodule Operative Surgical Procedures Organ Organogenesis Pathologic Pathway interactions Patients Pattern Performance Phenotype Plasma Process Proto-Oncogenes RNA Regulation Resectable Resected Residual Tumors Residual state Role Sampling Sensory Signal Transduction Skin Small RNA Specificity Staging Structure Technology Testing Time Tissue Sample Tissues Tumor Debulking Tumor Suppressor Proteins Tumor Tissue Woman Work anticancer research base cDNA Library candidate marker carcinogenesis cell motility chemotherapy clinical phenotype deafness gastrulation in vivo minimally invasive neoplastic cell novel polarized cell prospective receptor repository research study response tumor

项目摘要

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.

上皮细胞的功能需要正确的极性。它们的极性和模式是在器官发生上皮细胞通常在两个轴上极化，即在顶-基底外侧轴上和在细胞平面上极化。称为平面细胞极化或PCP。五氯苯酚的典型例子包括哺乳动物的皮肤或内部器官，例如内耳上皮及其感觉纤毛，以及昆虫的表皮结构，无脊椎动物五氯苯酚在果蝇体内的建立为研究五氯苯酚的测定提供了范例，极化单元形状的协调通常改变。PCP由远程信号协调，在激活卷曲（Fz）受体及其相关的信号级联（Fz/PCP信号）。的 Fz/PCP途径在整个进化过程中是保守的，并且还调节协调的蛋白质的其他几个方面。细胞极化，包括哺乳动物原肠胚形成期间的定向细胞迁移。值得注意的是，Fz/PCP ^信号传导与经典的Wnt/Fz-^连环蛋白途径不同。信号特异性的调节这两种途径之间由相同的受体激活的关系目前还知之甚少，但对于发展和疾病。此外，Fz/PCP信号传导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还不清楚。的范围本申请旨在研究新发现的五氯苯酚测定所需基因的具体作用，细胞形状变化协调。它们在Fz/PCP信号传导和/或细胞极化事件中的功能将被详细描述。进行了基因和生化研究。结合果蝇体内研究、细胞培养将利用分析和生化实验来实现这些目标。五氯苯酚的工艺建立和Wnt/Fz信号传导与几种医学异常（包括耳聋）有关。内耳上皮细胞的情况）和癌症（该途径的几种成分是原癌基因或肿瘤抑制剂）。因此，在这个应用程序中获得的信息将促进我们对细胞的理解，极化和图案化，并且将具有医学相关性，特别是对于致癌作用的研究。