Metastases cause major morbidities and nearly all of deaths in patients with breast cancer and other solid tumors. Our preliminary studies point to an intracellular signaling molecule, GIV, as a central determinant of metastatic potential of breast cancer cells. GIV integrates signals from multiple biochemical and mechanical inputs, placing this molecule as a central hub for key processes driving metastasis. In the parental RO1, we propose to investigate functions of GIV in breast cancer metastasis through a combination of cell-based assays and mouse models. We expect these studies to establish GIV as a potential predictive biomarker and therapeutic target for breast cancer. The research re-entry supplement will support the applicant and her return to a research career. The applicant will participate in all aspects of the proposed research, including planning experiments, analyzing data, and publishing manuscripts. She will learn new experimental methods focused on multi-scale, quantitative microscopy to complement her existing skills in cell and molecular biology. The supplement will enable the applicant to successfully transition back into a successful career in biomedical research.