Regulation of Normal and Cancer Cell Migration
We discovered that Arg is a key regulator of actin-based cell edge protrusions in several cellular contexts. Arg interacts with and regulates N-WASp and cortactin, both key regulators of the Arp2/3 complex to promote cell edge protrusion. We have recently discovered that in invasive breast cancer, Arg plays a key role in the formation of specialized actin-rich protrusions. These protrusions, termed invadopodia, mediate penetration of basement membranes and extracellular matrix to allow tumor cells to invade surrounding tissue. A major focus is to develop new methods to target these mechanisms to block invadopodial function and prevent tumor cell spread.
We also identified the Rho inhibitor p190RhoGAP as a major Arg substrate and demonstrated that Arg signaling through p190RhoGAP attenuates cell contractility and net cell migration. This has led us to the more general question of how cells translate adhesion cues and information on substrate compliance into changes in contractile/traction forces that lead to directed cell migration, which we aim to model by measuring migration on surfaces with different compliance.