MYOGEF IN CANCER CELL MIGRATION AND MOUSE EMBRYOGENESIS

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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.