Plasticity of cell migration: a multiscale tuning model

Friedl, Peter; Wolf, Katarina

doi:10.1083/jcb.200909003

Cited by 1,187 publications

(1,031 citation statements)

References 90 publications

(180 reference statements)

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“…Rac GTPase activity critically regulates pseudopodial protrusions and mesenchymal cell migration in 3D gels (Sanz-Moreno et al, 2008;Friedl and Wolf, 2010), separately confirmed in the cell lines used in the present study by the use of dominant-negative Rac. Downstream from Rac, Arp2/3 initiates short-branched actin filaments that push against the cell membrane, leading to membrane protrusion.…”

Section: Discussionsupporting

confidence: 74%

“…Tm5NM1-mediated changes to cell morphology and Src kinase activity A characteristic feature of mesenchymal migration in 3D cultures is the extension of long membrane processes in the direction of migration (as in Figure 1a), referred to as pseudopodia (Friedl and Wolf, 2010). We observed that the majority of the cells overexpressing Tm5NM1 failed to extend pseudopodia.…”

Section: Tm5nm1 Inhibits Mesenchymal Migrationmentioning

confidence: 72%

“…In contrast, amoeboid migration is characterized by rounded cell morphology and is associated with non-apoptotic plasma membrane blebbing (Sahai and Marshall, 2003). Rapid expansion and contraction allow amoeboid cells to squeeze through obstructing matrix, and this is highly dependant on actomyosin contractility (Sahai and Marshall, 2003;Sanz-Moreno et al, 2008;Friedl and Wolf, 2010). The migration of amoeboid cells is facilitated by the RhoA GTPase effector molecule Rho-associated kinase (ROCK), independent of matrix metalloprotease activity and less dependant on integrin receptor adhesion to the extracellular matrix (Friedl andWolf, 2003, 2010;Carragher et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility

et al. 2010

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Cell migration is an integral component of metastatic disease. The ability of cells to transit between mesenchymal and amoeboid modes of migration has complicated the development of successful therapies designed to target cell migration as a means of inhibiting metastasis. Therefore, investigations of the mechanisms that regulate cell migration and render cells stationary are necessary. Tropomyosins are actin-associating proteins that regulate the activity of several effectors of actin filament dynamics. Previously, we have shown that the tropomyosin isoform Tm5NM1 stabilizes actin filaments and inhibits cell migration in a two-dimensional culture system. Here, we show that Tm5NM1 inhibits the mesenchymal migration of multiple cell lines in an isoform-specific manner. Tm5NM1 stimulates the downregulation of Src kinase activity and a rounded or elliptical morphology in threedimensional collagen gels, and cells have dramatically reduced capacity to form pseudopodia. Importantly, we find that Tm5NM1 inhibits both the mesenchymal to amoeboid and amoeboid to mesenchymal transitions. Collectively, our data suggest that mimicking the action of Tm5NM1 overexpression represents an approach for effectively inhibiting the mesenchymal mode of migration.

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Section: Discussionsupporting

confidence: 74%

Section: Tm5nm1 Inhibits Mesenchymal Migrationmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility

et al. 2010

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“…b1 integrin is a well established player in cell motility (Friedl et al, 2004;Cordes and Park, 2007;Caswell et al, 2009;Friedl and Wolf, 2010). In this study, we show that its silencing, as well its inhibition, affects the invasive properties of A549 cells, both in terms of directional migration through Transwells and b1 integrin controls EGFR signaling V Morello et al in the ability to invade into 3D matrix.…”

Section: Discussionmentioning

confidence: 52%

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

et al. 2011

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Lung cancer is the leading cause of cancer death worldwide. The epidermal growth factor receptor (EGFR) represents the main target for non-small cell lung cancer (NSCLC) therapy, as its overexpression or constitutive activation contributes to malignancy and correlates with poor prognosis. Our previous work demonstrated that in epithelial cells b1 integrin is required for propagating EGFR signaling from the plasma membrane to the nucleus. In this study, we silenced b1 integrin in human NSCLC A549 cells. The b1 integrin-silenced cells show a defective activation of the EGFR signaling cascade, leading to decreased in vitro proliferation, enhanced sensitivity to cisplatin and Gefitinib, impaired migration and invasive behavior. Inhibitory effects on tumor growth and on the EGFR pathway were also observed in in vivo experiments. Moreover, b1 integrin silencing increases the amount of EGFR on the cell surface, suggesting that b1 integrin is required for efficient constitutive EGFR turnover at the cell membrane. Although the rate of EGF internalization and recycling is not affected in silenced cells, EGFR signaling is recovered only by expression of the Rab-coupling protein RCP, indicating that b1 integrin sustains the endocytic machinery required for EGFR signaling. Overall, these results show that b1 integrin is an essential regulator of EGFR signaling and tumorigenic properties of lung cancer cells, and that its silencing might represent an adjuvant approach to anti-EGFR therapy.

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“…2.2. Such forces are assumed to be viscous (Allena and Aubry 2012;Friedl and Wolf 2010;Phillipson et al 2006;Sakamoto et al 2011) and may be distinguished into a frontal (f f ) and a rear (f r ) force as follows:…”

Section: Intra-synchronizationmentioning

confidence: 99%

On the Mechanical Interplay Between Intra- and Inter-Synchronization During Collective Cell Migration: A Numerical Investigation

2013

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is an open access repository that collects the work of Arts et Métiers ParisTech researchers and makes it freely available over the web where possible. Abstract Collective cell migration is a fundamental process that takes place during several biological phenomena such as embryogenesis, immunity response, and tumorogenesis, but the mechanisms that regulate it are still unclear. Similarly to collective animal behavior, cells receive feedbacks in space and time, which control the direction of the migration and the synergy between the cells of the population, respectively. While in single cell migration intra-synchronization (i.e. the synchronization between the protrusion-contraction movement of the cell and the adhesion forces exerted by the cell to move forward) is a sufficient condition for an efficient migration, in collective cell migration the cells must communicate and coordinate their movement between each other in order to be as efficient as possible (i.e. intersynchronization). Here, we propose a 2D mechanical model of a cell population, which is described as a continuum with embedded discrete cells with or without motility phenotype. The decomposition of the deformation gradient is employed to reproduce the cyclic active strains of each single cell (i.e. protrusion and contraction). We explore different modes of collective migration to investigate the mechanical interplay between intra-and inter-synchronization. The main objective of the paper is to evaluate the efficiency of the cell population in terms of covered distance and how the

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Plasticity of cell migration: a multiscale tuning model

Cited by 1,187 publications

References 90 publications

The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility

The actin-associating protein Tm5NM1 blocks mesenchymal motility without transition to amoeboid motility

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

On the Mechanical Interplay Between Intra- and Inter-Synchronization During Collective Cell Migration: A Numerical Investigation

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