What makes cells move: requirements and obstacles for spontaneous cell motility

Abstract

Movement of individual cells and of cellular cohorts, chains or sheets requires physical forces that are established through interactions of cells with their environment. In vivo, migration occurs extensively during embryonic development and in adults during wound healing and tumorigenesis. In order to identify the molecular events involved in cell movement, in vitro systems have been developed. These have contributed to the definition of a number of molecular pathways put into play in the course of migratory behaviours, such as mesenchymal and amoeboid movement. More recently, our knowledge of migratory modes has been enriched by analyses of cells exploring and moving through three-dimensional (3D) matrices. While the cells' morphologies differ in 2D and 3D environments, the basic mechanisms that put a cellular body into motion are remarkably similar. Thus, in both 2D and 3D, the polarity of the migrating cell is initially defined by a specific subcellular localization of signalling molecules and components of molecular machines required for motion. While the polarization can be initiated either in response to extracellular signalling or be a chance occurrence, it is reinforced and sustained by positive feedback loops of signalling molecules. Second, adhesion to a substratum is necessary to generate forces that will propel the cell engaged in either mesenchymal or ameboid migration. For collective cell movement, intercellular coordination constitutes an additional requirement: a cell cohort remains stationary if individual cells pull in opposite directions. Finally, the availability of space to move into is a general requirement to set cells into motion. Lack of free space is probably the main obstacle for migration of most healthy cells in an adult multicellular organism. Thus, the requirements for cell movement are both intrinsic to the cell, involving coordinated signalling and interactions with molecular machines, and extrinsic, imposed by the physicochemical nature of the environment. In particular, the geometry and stiffness of the support act on a range of signalling pathways that induce specific cell migratory responses. These issues are discussed in the present review in the context of published work and our own data on collective migration of hepatocyte cohorts.

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

“…Migratory cells form a stable sub-population of microtubules at the leading edge to reorient the microtubule organizing center (MTOC) between the nucleus and the leading edge to create a polarized microtubule array that directs vesicular trafficking and maintains cell shape [9,10,19]. Additionally, disruption of the microtubule network by nocodazole-induced microtubule catastrophe or taxol-mediated microtubule stabilization, results in a depolarized cell morphology and a dramatic reduction in both the rate and directionality of migration [2,20].…”

“…As such, an accumulation of evidence correlates an invasive and metastatic state with the dysregulation of signals involved in cell migration [5,7,9,15,19,35,37]. For example, interactions between αvβ3, α5β1 and α6β4 and receptor tyrosine kinases (RTKs) such as ErbB2 and EGFR have been shown to facilitate the proliferation and migration of tumor cells independently of positional constraints in breast cancer [38,39].…”

“…General Introduction exhibits cellular retraction [7,8]. Without the acquisition of front-rear polarity, protrusions would be able to form simultaneously in opposite directions, creating a relative cellular tug-ofwar which would effectively render migration impossible [9]. At the molecular level, cellular polarization can be regarded as a bi-product of the unequal distribution of signaling molecules, cytoskeletal elements such as actin and tubulin, as well as directed membrane trafficking and redistribution of adhesion receptors to the leading edge [7,10].…”

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

“…The movement of crawling cells-those that propel themselves by some form of molecular interaction with the substrate in order to transmit force to the substrate-is classified as either mesenchymal or amoeboid, depending on how the cell interacts mechanically with its environment [60]. The mesenchymal mode is used by cells such as fibroblasts that have a well-organized cytoskeleton, and use strong adhesions to transmit force to their surroundings via integrin-mediated adhesion complexes.…”

Fibroblast growth factor signalling controls successive cell behaviours during mesoderm layer formation in Drosophila

“…Some tissues migrate as epithelial structures, maintaining apical-basal polarity, whereas others undergo a transition to a mesenchymal state (EMT) prior to migration (Biname et al, 2010). Mesenchymal cells migrate individually or as a collective, in which cells can move relative to each other while engaging and disengaging cell contacts (Weijer, 2009).…”