Genetic Analysis of Egfr Signaling and Cell Adhesion

促进癌症研究的伙伴关系：NMSU和FHCRC(第1/2) 完整项目#7：EGFR信号和细胞黏附的遗传分析 詹妮弗·柯蒂斯(NMSU)/布鲁斯·埃德加(FHCRC) 摘要 是否发生转移可以决定癌症患者的生死，而且 癌细胞是否转移取决于它与其他细胞黏附的能力和倾向。这个 黏附连接中细胞黏附分子E-钙粘附素的存在和活性是细胞黏附分子完整性所必需的 上皮细胞，其调控对上皮源性结构的形态发生至关重要。不足为奇的是 未受调控的E-钙粘附素活性与高度恶性肿瘤的发生和发展有关 浸润性癌。但是，是什么调节E-钙粘附素的表达和活性呢？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， 调节果蝇两种上皮细胞E-钙粘附素的表达和差异细胞亲和力 想象中的圆盘。此外，EGFR信号转导和E-钙粘素功能在心肌梗死中具有相互联系的功能。 起源于翅膀和眼睛的结构，如翼静脉和小眼的形态发生 分别为光盘。小分子GTP酶Rap1也影响E-钙粘蛋白的定位和 翅膀和眼睛发育过程中依赖于EGFR的细胞类型的分化。为了努力澄清 EGFR、Rap1和E-cadherin之间的关系，我们将使用功能损失和功能获得的方法来 确定RAP1在发育中的翼和眼想象盘中所起的作用。我们还将使用基于突变的 探讨E-钙粘附素介导的黏附对EGFR信号转导的影响。我们将使用Rap1 功能获得表型以筛选参与控制E-钙粘附素的基因。最后，我们将使用 基于微阵列的策略，以确定EGFR信号通路和Rap1的转录靶点。这个 果蝇和脊椎动物在这些发育过程中的显著相似性表明 我们的发现将导致抗击癌症的新策略。

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.