XB-ART-49726
J Cell Biol
July 7, 2014;
206
(1):
113-27.
In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity.
Abstract
Collective cell migration (CCM) and epithelial-mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell-cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell-cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like-to-fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness.
PubMed ID: 25002680
PMC ID: PMC4085712
Article link: J Cell Biol
Grant support: [+]
BB/D017521/1 Biotechnology and Biological Sciences Research Council , BB/F019769/1 Biotechnology and Biological Sciences Research Council , G0801145 Medical Research Council , G117/506 Medical Research Council , MR/J000655/1 Medical Research Council , Wellcome Trust , MRC_G0801145 Medical Research Council , MRC_G117/506 Medical Research Council , BB_BB/D017521/1 Biotechnology and Biological Sciences Research Council
Species referenced: Xenopus laevis
Genes referenced: cdh2 ctnnb1 ctnnd1 dlx2 enpp2 fli1 foxd3 gnl3 itk lpar1 lpar2 pxn rab5a rdx snai2 twist1 vcl wnt8a
Antibodies: Cdh2 Ab3 Ctnnb1 Ab5 Vcl Ab1
Morpholinos: enpp2 MO1 lpar1 MO2 lpar2 MO2
Article Images: [+] show captions
References [+] :
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Theveneau, Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. 2012, Pubmed , Xenbase
Thiery, Epithelial-mesenchymal transitions in development and disease. 2009, Pubmed
Umezu-Goto, Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. 2002, Pubmed
Urh, HaloTag, a Platform Technology for Protein Analysis. 2012, Pubmed
Wheelock, Cadherin switching. 2008, Pubmed
Wirtz, The physics of cancer: the role of physical interactions and mechanical forces in metastasis. 2011, Pubmed
Xiang, Lysophospholipid receptor activation of RhoA and lipid signaling pathways. 2012, Pubmed
Yonemura, alpha-Catenin as a tension transducer that induces adherens junction development. 2010, Pubmed
Aybar, Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. 2002, Pubmed , Xenbase
Barriga, The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition. 2013, Pubmed , Xenbase
Belmadani, The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors. 2005, Pubmed
Belmadani, The chemokine SDF-1/CXCL12 regulates the migration of melanocyte progenitors in mouse hair follicles. 2009, Pubmed
Bowes, Xenbase: a Xenopus biology and genomics resource. 2008, Pubmed , Xenbase
Carmona-Fontaine, Complement fragment C3a controls mutual cell attraction during collective cell migration. 2011, Pubmed , Xenbase
Carmona-Fontaine, Contact inhibition of locomotion in vivo controls neural crest directional migration. 2008, Pubmed , Xenbase
Clay, Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition. 2013, Pubmed
Contos, Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. 2000, Pubmed
Contos, Lysophosphatidic acid receptors. 2000, Pubmed
Contos, Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). 2002, Pubmed
Davies, Cancer as a dynamical phase transition. 2011, Pubmed
DeSimone, The Xenopus embryo as a model system for studies of cell migration. 2004, Pubmed , Xenbase
Doxzen, Guidance of collective cell migration by substrate geometry. 2013, Pubmed
Duband, Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest. 2010, Pubmed
Foty, The differential adhesion hypothesis: a direct evaluation. 2005, Pubmed
Friedl, Classifying collective cancer cell invasion. 2012, Pubmed
García, Micro-molding for poly(dimethylsiloxane) microchips. 2006, Pubmed
Grashoff, Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. 2010, Pubmed
Groysman, A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells. 2008, Pubmed
Hanahan, Hallmarks of cancer: the next generation. 2011, Pubmed
Houben, Autotaxin and LPA receptor signaling in cancer. 2011, Pubmed
Huang, Lysophosphatidic acid modulates the association of PTP1B with N-cadherin/catenin complex in SKOV3 ovarian cancer cells. 2013, Pubmed
Ishiyama, An autoinhibited structure of α-catenin and its implications for vinculin recruitment to adherens junctions. 2013, Pubmed
Kabla, Collective cell migration: leadership, invasion and segregation. 2012, Pubmed
Kam, Cadherin-bound beta-catenin feeds into the Wnt pathway upon adherens junctions dissociation: evidence for an intersection between beta-catenin pools. 2009, Pubmed
Kasemeier-Kulesa, CXCR4 controls ventral migration of sympathetic precursor cells. 2010, Pubmed
Kinoshita, Phosphate-binding tag, a new tool to visualize phosphorylated proteins. 2006, Pubmed
Kuriyama, A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways. 2009, Pubmed , Xenbase
Ladoux, Physically based principles of cell adhesion mechanosensitivity in tissues. 2012, Pubmed
Lim, Epithelial-mesenchymal transitions: insights from development. 2012, Pubmed
Lin, Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance. 2010, Pubmed
Liu, Lysophosphatidic Acid disrupts junctional integrity and epithelial cohesion in ovarian cancer cells. 2012, Pubmed
Los, The HaloTag: a novel technology for cell imaging and protein analysis. 2006, Pubmed
Mayor, The neural crest. 2013, Pubmed , Xenbase
Mills, The emerging role of lysophosphatidic acid in cancer. 2003, Pubmed
Miyake, Actomyosin tension is required for correct recruitment of adherens junction components and zonula occludens formation. 2006, Pubmed
Monsoro-Burq, Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals. 2003, Pubmed , Xenbase
Moolenaar, The ins and outs of lysophosphatidic acid signaling. 2004, Pubmed
Nandadasa, N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements. 2009, Pubmed , Xenbase
Nguyen, Metastasis: from dissemination to organ-specific colonization. 2009, Pubmed
Ogata, TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis. 2007, Pubmed , Xenbase
Olesnicky Killian, A role for chemokine signaling in neural crest cell migration and craniofacial development. 2009, Pubmed
Polyak, Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. 2009, Pubmed
Powell, Riding the crest of the wave: parallels between the neural crest and cancer in epithelial-to-mesenchymal transition and migration. 2013, Pubmed
Roszik, AccPbFRET: an ImageJ plugin for semi-automatic, fully corrected analysis of acceptor photobleaching FRET images. 2008, Pubmed
Rørth, Collective cell migration. 2009, Pubmed
Sasai, Requirement of FoxD3-class signaling for neural crest determination in Xenopus. 2001, Pubmed , Xenbase
Sauka-Spengler, A gene regulatory network orchestrates neural crest formation. 2008, Pubmed
Smicun, S1P and LPA have an attachment-dependent regulatory effect on invasion of epithelial ovarian cancer cells. 2007, Pubmed
Sumida, Myosin II activity dependent and independent vinculin recruitment to the sites of E-cadherin-mediated cell-cell adhesion. 2011, Pubmed
Taguchi, Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping. 2011, Pubmed
Tanaka, Nm23-H1 regulates contact inhibition of locomotion, which is affected by ephrin-B1. 2012, Pubmed
Tao, G-protein-coupled signals control cortical actin assembly by controlling cadherin expression in the early Xenopus embryo. 2007, Pubmed , Xenbase
Theveneau, Chase-and-run between adjacent cell populations promotes directional collective migration. 2013, Pubmed
Theveneau, Collective chemotaxis requires contact-dependent cell polarity. 2010, Pubmed , Xenbase
Theveneau, Collective cell migration of epithelial and mesenchymal cells. 2013, Pubmed
Theveneau, Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. 2012, Pubmed , Xenbase
Thiery, Epithelial-mesenchymal transitions in development and disease. 2009, Pubmed
Umezu-Goto, Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. 2002, Pubmed
Urh, HaloTag, a Platform Technology for Protein Analysis. 2012, Pubmed
Wheelock, Cadherin switching. 2008, Pubmed
Wirtz, The physics of cancer: the role of physical interactions and mechanical forces in metastasis. 2011, Pubmed
Xiang, Lysophospholipid receptor activation of RhoA and lipid signaling pathways. 2012, Pubmed
Yonemura, alpha-Catenin as a tension transducer that induces adherens junction development. 2010, Pubmed