title: Rho GTPases in collective cell migration.
abstract: The family of Rho GTPases are intracellular signal transducers that link cell surface signals to multiple intracellular responses. They are best known for their role in regulating actin dynamics required for cell migration, but in addition control cell-cell adhesion, polarization, vesicle trafficking, and the cell cycle. The roles of Rho GTPases in single mesenchymal cell migration are well established and rely on Cdc42- and Rac-dependent cell protrusion of a leading edge, coupled to Rho-dependent contractility required to move the cell body forward. In cells migrating collectively, cell-cell junctions are maintained, and migrating leader cells are mechanically coupled to, and coordinate, migration with follower cells. Recent evidence suggests that Rho GTPases provide multifunctional input to collective cell polarization, cell-cell interaction, and migration. Here, we discuss the role of Rho GTPases in initiating and maintaining front-rear, apical-basal cell polarization, mechanotransduction, and cell-cell junction stability between leader and follower cells, and how these roles are integrated in collective migration. Thereby, spatiotemporal fine-tuning of Rho GTPases within the same cell and among cells in the cell group are crucial in controlling potentially conflicting, divergent cell adhesion and cytoskeletal functions to achieve supracellular coordination and mechanocoupling.
authors: Department of Cell Biology; Radboud University Medical Center; Nijmegen, the Netherlands.
authors: Mirjam M
authors: MM
authors: Zegers
authors: Department of Cell Biology; Radboud University Medical Center; Nijmegen, the Netherlands; David H. Koch Center for Applied Research of Genitourinary Cancers; Department of Genitourinary Medical Oncology; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Cancer Genomics Centre Netherlands; Utrecht, the Netherlands.
authors: Peter
authors: P
authors: Friedl
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D006801:Humans; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Rac; Rho; cell adhesion; cell migration; collective migration