MYOGEF IN CANCER CELL MIGRATION AND MOUSE EMBRYOGENESIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 由于不受控制的细胞迁移引起的肿瘤转移标志着良性肿瘤和恶性肿瘤之间的区别，并且是癌症患者死亡的主要原因之一。小GT3蛋白定位于细胞的前缘，在那里它们调节细胞骨架重塑和细胞迁移。然而，在很大程度上不知道这些小的GT3蛋白如何在迁移细胞的前部定位和激活。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，在响应细胞外信号，MyoGEF定位到迁移细胞的前面，MyoGEF调节小GTdR蛋白的活性，反过来，调节肌动蛋白细胞骨架重塑和细胞迁移。我们进一步假设MyoGEF对小鼠的正常细胞迁移很重要。我们提出了两个具体的目标来检验我们的中心假设。在具体目标#1中，我们将测试我们的工作假设，即MyoGEF可以激活小GTdR蛋白，反过来，诱导迁移细胞前部的肌动蛋白细胞骨架重塑。在具体目标#2中，我们将测试我们的工作假设，即MyoGEF消融将影响正常细胞迁移，导致胚胎发生期间的异常。我们预期的研究结果应该提供重要的信息，从MyoGEF到Rho到肌动蛋白细胞骨架的信号级联反应，它在迁移细胞的前面起作用并调节细胞迁移。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 cell's 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.