The role of p120 catenin in mammary development and breast cancer
Kurley, Sarah Jean
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2012-04-04
Abstract
Cadherins and catenins are important regulators of tissue homeostasis and cancer. Here, we report critical roles for p120 catenin (p120) in mammary development and breast cancer. In the untransformed gland, p120 ablation delays ductal outgrowth and p120 null cells are rapidly excluded from the developing gland. We have traced the requirement of p120 to its cadherin-stabilizing function, which is necessary for collective migration of terminal end buds and branching morphogenesis. In a mouse model of breast cancer, mosaic p120 ablation induces an increase in size and number of pulmonary metastasis without affecting primary tumor growth. This augmentation is likely the result of a pro-metastatic microenvironment generated by p120 null cells, namely increased macrophages of the M2 phenotype, myofibroblasts, and collagen deposition. Paradoxically, p120 null cells themselves are metastasis deficient, specifically in late stages of the metastatic cascade. We propose that p120 is a key mediator of cellular plasticity and provides mechanisms to overcome the different challenges encountered by both the developing mammary epithelium and metastatic breast cancer cells.