scholarly journals P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

2016 ◽  
Vol 212 (2) ◽  
pp. 199-217 ◽  
Author(s):  
Cédric Plutoni ◽  
Elsa Bazellieres ◽  
Maïlys Le Borgne-Rochet ◽  
Franck Comunale ◽  
Agusti Brugues ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Biology ◽  
Cell Polarization ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Tumor Aggressiveness ◽  
And Migration ◽  
Cell Cell

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

scholarly journals ERK-mediated mechanochemical waves direct collective cell polarization

2019 ◽  
Author(s):  
Naoya Hino ◽  
Leone Rossetti ◽  
Ariadna Marín-Llauradó ◽  
Kazuhiro Aoki ◽  
Xavier Trepat ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarization ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Force Transmission ◽  
Long Distance ◽  
Erk Activation ◽  
Guidance Cues ◽  
Cell Cell

AbstractDuring collective migration of epithelial cells, the migration direction is aligned over a large, tissue-scale expanse. Although the collective cell migration is known to be directed by mechanical forces transmitted via cell-cell junctions, it remains elusive how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve collective movements. Here we show that intercellular coupling of extracellular signal-regulated kinase (ERK)-mediated mechanochemical feedback in individual cells yields long-distance transmission of guidance cues. Mechanical stretch activates ERK through epidermal growth factor receptor (EGFR) activation, and the ERK activation triggers cell contraction. In addition, the contraction of the activated cell pulls neighboring cells via cell-cell junctions, evoking another round of ERK activation and contraction in the neighbors. Furthermore, anisotropic contraction based on front-rear cell polarization guarantees unidirectional propagation of ERK activation waves, and in turn, the ERK activation waves direct multicellular alignment of the polarity, leading to long-range ordered migration. Our findings reveal that mechanical forces mediate intercellular signaling underlying sustained transmission of guidance cues for collective cell migration.

scholarly journals Collective cell migration requires suppression of actomyosin at cell–cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6

2010 ◽  
Vol 13 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Cristina Hidalgo-Carcedo ◽  
Steven Hooper ◽  
Shahid I. Chaudhry ◽  
Peter Williamson ◽  
Kevin Harrington ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Cell Cell

scholarly journals Role of P120 Ras-Gap in Directed Cell Movement

2000 ◽  
Vol 149 (2) ◽  
pp. 457-470 ◽  
Author(s):  
Sarang V. Kulkarni ◽  
Gerald Gish ◽  
Peter van der Geer ◽  
Mark Henkemeyer ◽  
Tony Pawson
Keyword(s):  
Cell Polarity ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Actin Stress Fiber ◽  
Dependent Manner ◽  
Directional Movement ◽  
Complete Cell ◽  
And Migration

We have used cell lines deficient in p120 Ras GTPase activating protein (Ras-GAP) to investigate the roles of Ras-GAP and the associated p190 Rho-GAP (p190) in cell polarity and cell migration. Cell wounding assays showed that Ras-GAP–deficient cells were incapable of establishing complete cell polarity and migration into the wound. Stimulation of mutant cells with growth factor rescued defects in cell spreading, Golgi apparatus fragmentation, and polarized vesicular transport and partially rescued migration in a Ras-dependent manner. However, for directional movement, the turnover of stress fibers and focal adhesions to produce an elongate morphology was dependent on the constitutive association between Ras-GAP and p190, independent of Ras regulation. Disruption of the phosphotyrosine-mediated Ras-GAP/p190 complex by microinjecting synthetic peptides derived from p190 sequences in wild-type cells caused a suppression of actin filament reorientation and migration. From these observations we suggest that although Ras-GAP is not directly required for motility per se, it is important for cell polarization by regulating actin stress fiber and focal adhesion reorientation when complexed with 190. This observation suggests a specific function for Ras-GAP separate from Ras regulation in cell motility.

Cell Polarity and Migration: Emerging Role for the Endosomal Sorting Machinery

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 171-180 ◽  
Author(s):  
Viola Hélène Lobert ◽  
Harald Stenmark
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
Cell Polarity ◽  
Tumor Suppressors ◽  
Potential Role ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Viral Budding ◽  
And Migration

The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in the regulation of endosomal sorting, cell division, viral budding, autophagy, and cell signaling. Here, we review recent evidence that implicates ESCRTs in cell polarity and cell migration, and discuss the potential role of ESCRTs as tumor suppressors.

scholarly journals Force transduction by cadherin adhesions in morphogenesis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1044 ◽  
Author(s):  
Willem-Jan Pannekoek ◽  
Johan de Rooij ◽  
Martijn Gloerich
Keyword(s):  
Adherens Junctions ◽  
Cell Behavior ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Cellular Behaviors ◽  
Intracellular Response ◽  
Cell Adhesions ◽  
Cell Intercalation ◽  
Cell Cell

Mechanical forces drive the remodeling of tissues during morphogenesis. This relies on the transmission of forces between cells by cadherin-based adherens junctions, which couple the force-generating actomyosin cytoskeletons of neighboring cells. Moreover, components of cadherin adhesions adopt force-dependent conformations that induce changes in the composition of adherens junctions, enabling transduction of mechanical forces into an intracellular response. Cadherin mechanotransduction can mediate reinforcement of cell–cell adhesions to withstand forces but also induce biochemical signaling to regulate cell behavior or direct remodeling of cell–cell adhesions to enable cell rearrangements. By transmission and transduction of mechanical forces, cadherin adhesions coordinate cellular behaviors underlying morphogenetic processes of collective cell migration, cell division, and cell intercalation. Here, we review recent advances in our understanding of this central role of cadherin adhesions in force-dependent regulation of morphogenesis.

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