P-cadherin-mediated Rho GTPase regulation during collective cell migration

Plutoni, Cédric; Bazellières, Elsa; Gauthier-Rouvière, Cécile

doi:10.1080/21541248.2016.1173772

Cited by 9 publications

(7 citation statements)

References 51 publications

(60 reference statements)

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“…As far as the cooperation of various cell types inside organoids is concerned, one can take into account the reorganization of adherens junctions and the force of transmission through them. It was demonstrated that remodeling of adherens junctions controls cell-cell cooperation during collective cell migration of MDCKII monolayers by the α-catenin-related mechanism (Matsuzawa et al 2018) and some studies point to the specific role of various cadherins, e.g., E-cadherin and P-cadherin, in collective cell movement in 3D (Plutoni et al 2016). Similarly, atypical Fat2 cadherin of Drosophila melanogaster is supposed to regulate collective cell movement during tissue rotation (Squarr et al 2016).…”

Section: Discussionmentioning

confidence: 99%

The migration and fusion events related to ROCK activity strongly influence the morphology of chicken embryo intestinal organoids

2018

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The method of organoid culture has become a tool widely used in gastrointestinal research, but so far, the migration of organoids derived from gut epithelium and formed in 3D Matrigel matrix has not been reported and studied. The intestinal epithelial tissue derived from 19-day-old chicken embryo was cultured in Matrigel and the dynamic properties of the forming organoids were analyzed by time-lapse image analysis. It was observed that about one in ten organoids actively moved through the matrix, at a speed of 10–20 μm/h. Moreover, rotation was observed in the majority of organoids that did not migrate long distances. The fusion events took place between organoids, which collided during the movement or growth. In our previous paper, we showed that the presence of Toll-like receptor 4 ligand, Escherichia coli lipopolysaccharide (LPS, 1 μg/ml), increased the mean organoid diameter. Here, we confirm this result and demonstrate that the Rho-associated protein kinase (ROCK) inhibitor Y-27632 (10 μM) did not completely abolish organoid migration, but prevented the fusion events, in both LPS-treated and untreated cultures. In consequence, in the presence of Y-27632, the differences between cultures incubated with and without LPS were not visible. We conclude that migration and fusion of organoids may influence their morphology and suggest that these phenomena should be taken into account during the design of experimental settings. Electronic supplementary material The online version of this article (10.1007/s00709-018-1312-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The migration and fusion events related to ROCK activity strongly influence the morphology of chicken embryo intestinal organoids

2018

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“…Finally, we sought to investigate if the observed transdifferentiation of anillin-depleted MDA-MB-231 cells plays a causal role in inhibiting cell migration and invasion. We focused on cadherin overexpression since both E-and P-cadherins are known regulators of cell migration [52,53]. Either E-cadherin or P-cadherin were transiently downregulated in control and anillin-depleted MDA-MB-231 cells and effects of their depletion on cell motility were determined using the wound closure and Matrigel invasion assays.…”

Section: Downregulation Of E-cadherin Reverses Attenuated Migrating Amentioning

confidence: 99%

Anillin regulates breast cancer cell migration, growth, and metastasis by non-canonical mechanisms involving control of cell stemness and differentiation

et al. 2020

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Background: Breast cancer metastasis is driven by a profound remodeling of the cytoskeleton that enables efficient cell migration and invasion. Anillin is a unique scaffolding protein regulating major cytoskeletal structures, such as actin filaments, microtubules, and septin polymers. It is markedly overexpressed in breast cancer, and high anillin expression is associated with poor prognosis. The aim of this study was to investigate the role of anillin in breast cancer cell migration, growth, and metastasis. Methods: CRISPR/Cas9 technology was used to deplete anillin in highly metastatic MDA-MB-231 and BT549 cells and to overexpress it in poorly invasive MCF10AneoT cells. The effects of anillin depletion and overexpression on breast cancer cell motility in vitro were examined by wound healing and Matrigel invasion assays. Assembly of the actin cytoskeleton and matrix adhesion were evaluated by immunofluorescence labeling and confocal microscopy. In vitro tumor development was monitored by soft agar growth assays, whereas cancer stem cells were examined using a mammosphere formation assay and flow cytometry. The effects of anillin knockout on tumor growth and metastasis in vivo were determined by injecting control and anillin-depleted breast cancer cells into NSG mice. Results: Loss-of-function and gain-of-function studies demonstrated that anillin is necessary and sufficient to accelerate migration, invasion, and anchorage-independent growth of breast cancer cells in vitro. Furthermore, loss of anillin markedly attenuated primary tumor growth and metastasis of breast cancer in vivo. In breast cancer cells, anillin was localized in the nucleus; however, knockout of this protein affected the cytoplasmic/cortical events, e.g., the organization of actin cytoskeleton and cell-matrix adhesions. Furthermore, we observed a global transcriptional reprogramming of anillin-depleted breast cancer cells that resulted in suppression of their stemness and induction of the mesenchymal to epithelial trans-differentiation. Such trans-differentiation was manifested by the upregulation of basal keratins along with the increased expression of E-cadherin and P-cadherin. Knockdown of E-cadherin restored the impaired migration and invasion of anillin-deficient breast cancer cells.

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“…Given RHOU’s dual and opposing effects on the epidermis’ intercellular and cell-substratum borders, we were especially intrigued by the prominence in RHOU’s interactome of the p21-activated serine-threonine kinases, PAK1 and PAK2, and the guanine nucleotide exchange protein ARHGEF7 (β-PIX). These proteins are known to shuttle as a complex between adherens junctions, where tyrosine kinase receptor activity is silent and focal adhesions, where it is active (Livshits et al, 2012; Plutoni et al, 2016). Interestingly, EGFR was also present in our interactome (Supplementary file 6).…”

Section: Resultsmentioning

confidence: 99%

An RNAi screen unravels the complexities of Rho GTPase networks in skin morphogenesis

Laurin

Gomez

Levorse

et al. 2019

eLife

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During mammalian embryogenesis, extensive cellular remodeling is needed for tissue morphogenesis. As effectors of cytoskeletal dynamics, Rho GTPases and their regulators are likely involved, but their daunting complexity has hindered progress in dissecting their functions. We overcome this hurdle by employing high throughput in utero RNAi-mediated screening to identify key Rho regulators of skin morphogenesis. Our screen unveiled hitherto unrecognized roles for Rho-mediated cytoskeletal remodeling events that impact hair follicle specification, differentiation, downgrowth and planar cell polarity. Coupling our top hit with gain/loss-of-function genetics, interactome proteomics and tissue imaging, we show that RHOU, an atypical Rho, governs the cytoskeletal-junction dynamics that establish columnar shape and planar cell polarity in epidermal progenitors. Conversely, RHOU downregulation is required to remodel to a conical cellular shape that enables hair bud invagination and downgrowth. Our findings underscore the power of coupling screens with proteomics to unravel the physiological significance of complex gene families.

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P-cadherin-mediated Rho GTPase regulation during collective cell migration

Cited by 9 publications

References 51 publications

The migration and fusion events related to ROCK activity strongly influence the morphology of chicken embryo intestinal organoids

The migration and fusion events related to ROCK activity strongly influence the morphology of chicken embryo intestinal organoids

Anillin regulates breast cancer cell migration, growth, and metastasis by non-canonical mechanisms involving control of cell stemness and differentiation

An RNAi screen unravels the complexities of Rho GTPase networks in skin morphogenesis

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