Par-4 Regulation of Actomyosin Contractility as a Tumor Suppressive Mechanism in Breast Cancer

The long-term goal is to identify pathways regulating tumor progression, resistance to therapy, metastasis, and recurrence to improve treatment. The project uses conditional genetically engineered mouse (GEM) models of breast cancer to dissect dormancy and recurrence processes. Previous work identified Par-4's role in regulating breast cancer cell survival and recurrence, noting its downregulation in recurrent tumors and its association with poor therapy response and increased recurrence risk in women. This proposal will further explore the mechanism by which Par-4 acts as a tumor suppressor, specifically testing the hypothesis that Par-4 promotes cell death partly by inducing actomyosin contractility, contributing to its tumor suppressive functions. This will be investigated in the context of Par-4’s role in residual cell survival and invasive lobular cancer cells, aiming to uncover novel therapeutic intervention opportunities.