Genetic Analysis of Egfr Signaling and Cell Adhesion

Egfr 信号传导和细胞粘附的遗传分析

• 批准号: 7422091
• 负责人: JENNIFER R CURTISS
• 金额: $ 17.47万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7422091
• 关键词: Address; Adherens Junction; Adhesions; Affect; Affinity; Apical; Cancer Patient; Carcinoma; Cell Adhesion; Cell Adhesion Molecules; Cell physiology; Cells; Cessation of life; Complement; Data; Defect; Detection; Development; Developmental Process; Drosophila genome; Drosophila genus; E-Cadherin; Epidermal Growth Factor Receptor; Epithelial; Epithelium; Eye; Eye Development; Genes; Genetic; Goals; Guanosine Triphosphate Phosphohydrolases; Invasive; Lead; Life; Ligands; Malignant - descriptor; Malignant Neoplasms; Mediating; Membrane; Microarray Analysis; Modeling; Morphogenesis; Neoplasm Metastasis; Pathway interactions; Patients; Pattern; Phenotype; Photoreceptors; Play; Prevention; Process; RNA Interference; Receptor Protein-Tyrosine Kinases; Regulation; Role; Shotguns; Signal Pathway; Signal Transduction; Specific qualifier value; Staining method; Stains; Structure; Testing; Tissues; Transgenes; Veins; Vertebrates; Wing; abstracting; anticancer research; base; cancer cell; cell transformation; cell type; fight against; gain of function; genetic analysis; imaginal disc; loss of function; research study; small molecule

Partnership for the Advancement of Cancer Research: NMSU & FHCRC (1 of 2) Full Project #7: Genetic analysis of Egfr signaling and cell adhesion Jennifer Curtiss (NMSU) / Bruce Edgar (FHCRC) ABSTRACT Whether or not metastasis occurs can make the difference between life and death for a cancer patient, and whether or not a cancer cell metastasizes lies in its ability and propensity to adhere to other cells. The presence and activity of the cell adhesion molecule E-cadherin in adherens junctions is required for integrity of epithelia, and its regulation is critical for morphogenesis of epithelial-derived structures. Little wonder that unregulated E-cadherin activity has been implicated in development and progression of highly malignant invasive carcinomas. But what regulates E-cadherin expression and activity? We have discovered that the Epidermal Growth Factor Receptor (Egfr) signaling pathway, which is also associated with cancer cell invasion, regulates expression of E-cadherin and differential cell affinity in two Drosophila epithelia, the wing and eyeantennal imaginal discs. Furthermore, Egfr signaling and E-cadherin function have interrelated functions in the morphogenesis of structures such as the wing veins and ommatidia, which are derived from the wing and eye discs, respectively. The small molecule GTPase Rap1 also affects E-cadherin localization and the differentiation of Egfr-dependent cell types during both wing and eye development. In an effort to elucidate the relationships between Egfr, Rap1 and E-cadherin, we will use loss- and gain-of-function approaches to determine what role Rap1 plays in the developing wing and eye imaginal discs. We will also use a mutationbased approach to explore the effect of E-cadherin-mediated adhesion on Egfr signaling. We will use Rap1 gain-of-function phenotypes to screen for genes involved in controlling E-cadherin. Finally, we will use a microarray-based strategy to identify transcriptional targets of the Egfr signaling pathway and Rap1. The remarkable similarities between Drosophila and vertebrates in these developmental processes suggest that our discoveries will lead to new tactics in the fight against cancer.

促进癌症研究的合作伙伴关系：NMSU 和 FHCRC（2 中的 1） 完整项目#7：Egfr 信号传导和细胞粘附的遗传分析 詹妮弗·柯蒂斯 (NMSU) / 布鲁斯·埃德加 (FHCRC) 抽象的 是否发生转移可能关系到癌症患者的生死， 癌细胞是否转移取决于其粘附其他细胞的能力和倾向。这 粘附连接中细胞粘附分子 E-钙粘蛋白的存在和活性对于粘附连接的完整性是必需的 上皮细胞，其调节对于上皮衍生结构的形态发生至关重要。难怪 不受调节的 E-钙粘蛋白活性与高度恶性的发生和进展有关 侵袭性癌。但是什么调节 E-钙粘蛋白的表达和活性呢？我们发现， 表皮生长因子受体（Egfr）信号通路，也与癌细胞侵袭有关， 调节两种果蝇上皮（翅膀和眼触角）中 E-钙粘蛋白的表达和差异细胞亲和力 想象光盘。此外，Egfr 信号传导和 E-cadherin 功能在 翼静脉和小眼等结构的形态发生，这些结构源自翅膀和眼睛 光盘，分别。小分子 GTPase Rap1 也影响 E-钙粘蛋白定位和 Egfr 依赖性细胞类型在翅膀和眼睛发育过程中的分化。为了努力阐明 Egfr、Rap1 和 E-cadherin 之间的关系，我们将使用功能丧失和获得的方法来 确定 Rap1 在发育中的翅膀和眼睛成虫盘中发挥什么作用。我们还将使用基于突变的 方法探讨 E-钙粘蛋白介导的粘附对 Egfr 信号传导的影响。我们将使用 Rap1 功能获得表型来筛选参与控制 E-钙粘蛋白的基因。最后，我们将使用一个 基于微阵列的策略来识别 Egfr 信号通路和 Rap1 的转录靶标。这 果蝇和脊椎动物在这些发育过程中的显着相似性表明 我们的发现将带来抗击癌症的新策略。