1. How do tumor cells sense and respond to alteration in ECM structure and composition?
During oncogenic transformation, normal interactions with the ECM are profoundly altered, resulting in cells that lose their polarization and differentiation, lose anchorage dependent growth control, and acquire a migratory, invasive phenotype. To investigate the features of the ECM that are critical to these tumor-associated phenotypes, we use an in vitro 3D collagen gel model. Using this model, we determined that increasing the stiffness of the collagen matrix is sufficient to disrupt breast epithelial differentiation, increase cell proliferation and enhance invasion. However, the specific molecular players and signaling pathways that are regulated by ECM alterations, and how these pathways are involved in the progression of breast cancer is still relatively unknown. Therefore, part of the lab is focused on understanding how cells sense and respond to mechanical and compositional alterations of the extracellular matrix during cell invasion.