6th Annual Symposium
Physics of Cancer
Leipzig, Germany
September 7-9, 2015
Invited Talk
Mechanoregulation of Collective Cell Migration
Tamal Das1,2, Kai Safferling3,4, Sebastian Rausch1,2, Niels Grabe3,4, Heike Boehm1,2, Joachim P. Spatz1,2
1Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Stuttgart - 70569, Germany
2Department of Biophysical Chemistry, University of Heidelberg, Heidelberg - 69120, Germany
3Hamamatsu Tissue Imaging and Analysis (TIGA) Center, BIOQUANT, University of Heidelberg, Heidelberg - 69120, Germany
44 NCT National Center for Tumor Diseases, Department of Medical Oncology, University of Heidelberg, Heidelberg - 69120, Germany
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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 [1]. Collective movement of epithelial cells drives many important physiological processes including embryonic development, morphogenesis, cancer, and most importantly, wound healing [2]. 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 [3]. 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 [4].
[1]P. RorthFellow travellers: emergent properties of collective cell migration, Embo Reports (13, 11, 984-991) (2012)
[2]P. Friedl and D. GilmourCollective cell migration in morphogenesis, regeneration and cancer, Nature Reviews Molecular Cell Biology (10, 7, 445-457) (2009)
[3]T. Das, K. Safferling, S. Rausch, N. Grabe, H. Boehm, and J.P. SpatzA molecular mechanotransduction pathway regulates collective migration of epithelial cells, Nature Cell Biology (17, 3, 276-287) (2015)
[4]A. Zoch and H. MorrisonMerlin's wizardry guides cohesive migration, Nature Cell Biology (17, 3, 212-213) (2015)
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