Cellular heterogeneity of a tumor is critical to the progression of the malignant process, but the underlying mechanisms behind this phenomenon remain poorly understood. Moreover, since most studies relating to tumor heterogeneity focus on the genetic aspects of this phenomenon, the molecular and cellular physiological mechanisms are in many cases overlooked. In this project we investigate whether and how heterogeneities in the activity of cellular Ca2+ signaling and mechanosensing machineries produce different cellular behaviors in response to changes in the tumor microenvironment. We combine state of the art multidisciplinary in vitro and in vivo approaches to study the link between the metastatic potential of cancer cells and aberrant Ca2+ signaling and mechanosensing activity.