While the current data does not support formulating an integrative model, an attractive possibility is that PI3K lies upstream of myosin II in short-term contraction (e.g., in response to chemoattractants) and physiological scenarios under continuous stress (e.g., smooth muscle contraction to control blood pressure), whereas mechanical control of PI3K activity, i.e., myosin II upstream of PI3K, may be important in chronic deformation of tissue, e.g., cancer-induced tissue stiffening. This evidence concerns the gene PIK3CA and cancer.