A. Model of mammary duct organization, which can be perturbed by malignant transformation or changes in ECM stiffness. Together, these events lead to cancer cell invasion through PI3K, FAK and vinculin activation. B. Biophysical model of vinculin dependent adhesion signaling. Extracellular cues drive integrin activation, talin binding, and vinculin activation. Vinculin-talin-actin stabilization facilitates PI3K conversion of PIP2 to PIP3, activation of FAK and Akt, and intracellular signaling that leads to cancer cell invasion.