Regulation of Snail in Breast Cancer Progression and Metastasis

Transfer Proposal - Down-regulation of E-cadherin plays an important role in epithelial-mesenchymal transition (EMT), which is critical in normal development and disease states such as tissue fibrosis and metastasis. Our central hypothesis is that EPLlNI3 functions as a negative regulator for Snail; loss of expression of EPLlN(3 in breast cancer induces the stabilization and nuclear localization of Snail, thus triggering cell migration and metastasis of breast cancer. The long-term goal of this proposal is to characterize the functional regulation of Snail by EPLlN(3 in breast cancer and explore the prognostic value of EPLlNj3 and Snail as markers of metastasis for breast cancer. To test our central hypothesis and achieve the objective of this proposal, we have planned experiments with the following three Specific Aims: Aim 1: To delineate the regions on Snail and EPLlN(3 required for their association Aim 2: To determine whether the loss of EPLlN(3 enhances the stabilization of Snail Aim 3: To define the functional regulation of Snail and EPLlN(3 in mouse and human breast cancer