Deletion of the cytoplasmic domain of N-cadherin reduces, but does not eliminate, traction force-transmission

Lee, Eliot; Ewald, Makena L.; Sedarous, Mary; Kim, Timothy; Weyers, Brent W.; Truong, Rose Hong; Yamada, Sōichiro

doi:10.1016/j.bbrc.2016.08.173

Cited by 13 publications

(11 citation statements)

References 33 publications

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“…Unfortunately, our understanding of how N-cadherin influences cancer cell metastasis, and tumorigenesis in general, remains incomplete. Studies in cardiomyocytes, stromal cells and epithelial cancer-like cells have ascribed focal adhesion-like properties to N-cadherin including mechanotransduction and traction-force transmission [ 192 – 195 ]. Indeed, whether a ‘traction and propulsion’-type system, via homotypic N-cadherin mediated cell-cell contacts, is utilised by cancer cells to facilitate migration is intriguing and warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer

et al. 2018

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In many types of solid tumours, the aberrant expression of the cell adhesion molecule N-cadherin is a hallmark of epithelial-to-mesenchymal transition, resulting in the acquisition of an aggressive tumour phenotype. This transition endows tumour cells with the capacity to escape from the confines of the primary tumour and metastasise to secondary sites. In this review, we will discuss how N-cadherin actively promotes the metastatic behaviour of tumour cells, including its involvement in critical signalling pathways which mediate these events. In addition, we will explore the emerging role of N-cadherin in haematological malignancies, including bone marrow homing and microenvironmental protection to anti-cancer agents. Finally, we will discuss the evidence that N-cadherin may be a viable therapeutic target to inhibit cancer metastasis and increase tumour cell sensitivity to existing anti-cancer therapies.

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Section: Discussionmentioning

confidence: 99%

N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer

et al. 2018

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“…The protocol for E-cadherin coating was inspired from a previous study by Lee and colleagues 93 . Briefly, the cleaned glass coverslips were silanized with 10% 3-aminopropyl triethoxysilane (APTES, Sigma-Aldrich) in 100% ethanol for 10 minutes at RT, washed once in 100% ethanol and dried at 80°C for 10 minutes.…”

Section: Methodsmentioning

confidence: 99%

Myosin II isoforms play distinct roles in adherens junction biogenesis

Heuzé

Sankara

Dang

et al. 2019

Preprint

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29Adherens junction (AJ) assembly under force is essential for many biological processes like 30 epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The 31 acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and 32 remodelling of AJ. Here, we investigated the role of myosinII isoforms in epithelial junction 33 assembly. Myosin IIA (NMIIA) and Myosin IIB (NMIIB) differentially regulate biogenesis of 34 adherens junction through association with distinct actin networks. Analysis of junction 35 dynamics, actin organization, and mechanical forces of control and knockdown cells for 36 myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell 37 junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, 38 maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional 39 actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated 40 complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ. 41 42 Introduction 43 Tissue integrity and plasticity rely on cell-cell adhesion and cell contractility. The formation, 44 remodelling and disassembly of cell-cell adhesions are fundamental events accompanying all 45 stages of morphogenesis, tissue homeostasis and healing. Adherens junctions (AJ) mediated 46 by E-cadherin/catenin complexes are key elements of epithelial cell-cell adhesions and the 47 first ones to assemble upon contact initiation 1-3 . They provide strong mechanical coupling 48 between neighbouring cells through association with the acto-myosin cytoskeleton 4 . 49The assembly of de novo AJ is crucial for cell-cell rearrangement 5,6 , tissue closure 7 and the 50 maintenance of epithelial cell integrity during wound healing or cell extrusion 8-10 . During de 51 novo cell-cell contacts formation, initial contacts between facing lamellipodia induce immediate 52 clustering of cadherin molecules by trans-and cis-oligomerization [11][12][13][14] . Subsequent signalling 53 events involving RhoGTPases trigger local remodelling of the actin cytoskeleton through 54 Arp2/3-or formin-mediated actin polarization in the vicinity of AJs 15-17 . These cytoskeletal 55 rearrangements drive the expansion of cell-cell contacts and inter-cellular adhesion 56 strengthening 2,18,19 . 57Non-muscle Myosin II (NMII) has emerged as a fundamental player in force-generation and 58 force-transmission at AJ both in vitro and in vivo [20][21][22] . NMII is essential for epithelial tissue 59 architecture 23 , epithelial tissue morphogenesis 24 , tissue repair 25,26 and cell extrusion 27 . NMII 60 protects junctions from disassembly during development 28 and provides the mechanical 61 tugging force necessary for AJ reinforcement 29 . In endothelial cells, NMII is recruited early in 62 filopodia-mediated bridge bundles and its activity is required for accumulation of VE-cadherin 63 in nascent AJs 30 . In epithelial cells, NMII favours local...

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“…, 2015 ). In the case of hepatocyte growth factor–stimulated MDCK cells plated on N-cadherin substrates, depletion of the cytoplasmic domain does not completely abolish tractions ( Lee et al. , 2016 ), suggesting that alternative mechanisms may also contribute.…”

Section: The Mechanics Of Collectively Migrating Cell Groupsmentioning

confidence: 99%

Single and collective cell migration: the mechanics of adhesions

Pascalis

Etienne-Manneville

2017

MBoC

308

260

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Chemical and physical properties of the environment control cell proliferation, differentiation, or apoptosis in the long term. However, to be able to move and migrate through a complex three-dimensional environment, cells must quickly adapt in the short term to the physical properties of their surroundings. Interactions with the extracellular matrix (ECM) occur through focal adhesions or hemidesmosomes via the engagement of integrins with fibrillar ECM proteins. Cells also interact with their neighbors, and this involves various types of intercellular adhesive structures such as tight junctions, cadherin-based adherens junctions, and desmosomes. Mechanobiology studies have shown that cell–ECM and cell–cell adhesions participate in mechanosensing to transduce mechanical cues into biochemical signals and conversely are responsible for the transmission of intracellular forces to the extracellular environment. As they migrate, cells use these adhesive structures to probe their surroundings, adapt their mechanical properties, and exert the appropriate forces required for their movements. The focus of this review is to give an overview of recent developments showing the bidirectional relationship between the physical properties of the environment and the cell mechanical responses during single and collective cell migration.

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Deletion of the cytoplasmic domain of N-cadherin reduces, but does not eliminate, traction force-transmission

Cited by 13 publications

References 33 publications

N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer

N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer

Myosin II isoforms play distinct roles in adherens junction biogenesis

Single and collective cell migration: the mechanics of adhesions

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