6th Annual Symposium
Physics of Cancer
September 7-9, 2015
|PoC - Physics of Cancer - Annual Symposium|
Mechanoregulation of Collective Cell Migration
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Collective cell migration refers to the process of many cells migrating as cohesive units with each individual cell coordinating its own movement with that of its neighbors . Collective movement of epithelial cells drives many important physiological processes including embryonic development, morphogenesis, cancer, and most importantly, wound healing . Yet the molecular mechanism that ensures the correlated movement of several epithelial cells remained unknown for a long time. To this end, we have recently shown that a tumor suppressor protein, merlin, supports the collective migration of epithelial cells . Merlin acts as a biomechanical force-transducer and links the mechanical forces at the cell-cell junctions to cell movements in a migrating epithelial monolayer. In stationary epithelial monolayer, merlin localizes to cortical cell-cell junctions. During initiation of migration, a fraction of cortically localized merlin relocalizes to cell cytoplasm. This process is triggered by the pulling force of the leading cell, and it relies on the actomyosin-based cell contractility. Then in migrating cells, taking cue from these cell-cell pulling forces, merlin spatially polarizes Rac1 activation and lamellipodia formation. Together these events support the aligned and correlated motion of many cells. The results presented in this study, thus, provide a unique molecular mechanism delineating how cells convert intercellular forces to correlated cell movements. They also demonstrate that in absence of any perceptible long-range guidance cue, such as the gradient of chemoattractants, how local interactions give rise to collective dynamics at multicellular level. These observations, therefore, provide an analogy to the basic notion of collective movements observed in other levels of nature and have important implications in cancer biology and wound healing .