| Abstract | Once cancer cells dissociate from a primary tumor, metastatic progression depends on their ability to adhere to extracellular matrix (ECM) components and become motile cells that enter the circulation, invade distant organs, and establish secondary tumors. Much focus on the metastatic cascade has been in determining genetic and proteomic signatures of invasive tumor cells, however, how force-dependent molecular switches and cell tension affect invasiveness are less well understood. Here we describe the Rap1 GTPase as a molecular switch activated in response to changes in extracellular force. Activated Rap1-GTP binds a number of proteins that control integrin activation and actin dynamics at the cell membrane, thereby serving as a rheostat to balance intracellular tension to extracellular compliance and cues. I will discuss this role for Rap1 activation in the context of tumor cell motility and cell morphology at the single cell level. This will be related to how Rap1 activation and intracellular tension affect adhesion dynamics at the focal adhesion level in both 2 and 3-dimensional microenvironments. |
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