MYOGEF IN CANCER CELL MIGRATION AND MOUSE EMBRYOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肿瘤转移是由于细胞不受控制的迁移，它标志着良性肿瘤和恶性肿瘤的区别，是癌症患者死亡的主要原因之一。小的GTPase蛋白定位于细胞前沿，在那里它们调节细胞骨架重塑和细胞迁移。然而，很大程度上还不清楚这些小的GTPase蛋白是如何在迁移细胞的前部定位和激活的。我们的长期目标是了解调控细胞迁移的分子机制。我们的中心假设是，作为对细胞外信号的响应，MyoGlobal定位于迁移细胞的前端，在那里MyoGlobal调节小GTPase蛋白的活性，进而调节肌动蛋白细胞骨架的重塑和细胞迁移。我们进一步假设，MyoGlobal对于小鼠的正常细胞迁移是重要的。我们提出了两个具体的目标来检验我们的中心假设。在特定的目标#1中，我们将检验我们的工作假设，即Myogef可以激活小的GTP酶蛋白，进而诱导迁移细胞前端的肌动蛋白细胞骨架重构。在特定的目标#2中，我们将测试我们的工作假设，即去除Myogef将影响正常的细胞迁移，导致胚胎发育过程中的异常。我们预期的发现将提供重要的信息，关于从Myogef到Rho再到肌动蛋白细胞骨架的信号级联，肌动蛋白细胞骨架在迁移细胞的前端工作，并调节细胞迁移。最终，这些知识将使我们能够确定预防肿瘤转移的潜在分子策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tumor metastasis, which is due to uncontrolled cell migration, signifies the difference between a benign and malignant tumor and is one of the major reasons for death in cancer patients. Small GTPase proteins localize to the cells leading edge, where they regulate cytoskeletal remodeling and cell migration. However, it is largely unknown how these small GTPase proteins are localized and activated at the front of migrating cells. Our long-term goal is to understand the molecular mechanisms operative in regulating cell migration. Our central hypothesis is that, in response to extracellular signals, MyoGEF localizes to the front of migrating cells, where MyoGEF modulates the activity of small GTPase proteins that, in turn, regulate actin cytoskeleton remodeling and cell migration. We further hypothesize that MyoGEF is important for normal cell migration in mice. We propose two specific aims to test our central hypothesis. In Specific Aim #1, we will test our working hypothesis that MyoGEF can activate small GTPase proteins that, in turn, induce actin cytoskeleton remodeling at the front of migrating cells. In Specific Aim #2, we will test our working hypothesis that ablation of MyoGEF will affect normal cell migration, leading to abnormalities during embryogenesis. Our expected findings should provide important information regarding a signaling cascade from MyoGEF to Rho to actin cytoskeleton, which operates at the front of migrating cells and regulates cell migration. Ultimately, this knowledge will allow us to identify potential molecular strategies for the prevention of tumor metastasis.