Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

Ohsawa, Seiji; Vaughen, John; Igaki, Tatsushi

doi:10.1016/j.devcel.2018.01.009

Cited by 99 publications

(75 citation statements)

References 152 publications

(211 reference statements)

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“…The expression of these genes downregulates epithelial cadherins, disrupts apicobasal polarity (mediated by the aPKC/Par complex), disassembles AJs, and induces changes in cytoskeleton organization (Acloque et al, 2009; Lim & Thiery, 2012). A rearrangement of the actin-myosin cytoskeleton induces apical constriction of cells (generating a bottle-like shape), which detach from the epithelial sheet, break down the basal membrane, and invade a specific tissue as mesenchymal cells (Acloque et al, 2009; Lim & Thiery, 2012; Ohsawa, Vaughen, & Igaki, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Bilaterian-EMT has been a focus of study for decades as a mechanism to segregate different cell layers involved in a variety of different normal and pathological biological processes (Nieto, Huang, Jackson, & Thiery, 2016; Ohsawa et al, 2018). This process appears to depend on the fine regulation of snail expression levels and their temporal activity.…”

Section: Discussionmentioning

confidence: 99%

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Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm

Salinas‐Saavedra

Rock

Martindale

2017

Preprint

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Summary 25In triploblastic animals, Par proteins regulate cell-polarity and adherens junctions of both 26 ectodermal and endodermal epithelia. But, in embryos of the diploblastic cnidarian Nematostella 27 vectensis, Par proteins are eliminated altogether in the bifunctional endomesodermal epithelia. 28Using immunohistochemistry, CRISPR/Cas9, and overexpression of specific mRNAs, we describe 29 the functional association between Par proteins, ß-catenin, and snail genes in N. 30vectensis embryos. We demonstrate that the aPKC/Par complex regulates the localization of ß-31 catenin in the ectoderm by directing its role in cell adhesion, and that endomesodermal epithelia 32 are organized by a different cell adhesion system. We also show that snail genes, which are 33 mesodermal markers in bilaterians, are sufficient to downregulate Par proteins and translocate ß- 34catenin from the junctions to the cytoplasm in N. vectensis. These data provide insight into the 35 evolution of epithelial structure and the evolution of mesoderm in metazoan embryos. 37All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm

Salinas‐Saavedra

Rock

Martindale

2017

Preprint

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“…Epithelial cell sheets maintain an appropriate cell number and healthy tissue function through the apical extrusion of apoptotic or live cells [103][104][105]. Apical epithelial cell extrusion is associated with the activation of non-muscle myosin II (NMMII)-dependent contractility that, through pulling forces on cell-cell and cell-matrix adhesion, facilitates cell de-adhesion from basal lamina and subsequent translocation of cells to the apical portion of the epithelial sheet [33,34].…”

Section: Outgrowth Formationmentioning

confidence: 99%

Ovarian Cancer Dissemination—A Cell Biologist’s Perspective

Farsinejad

Cattabiani

Muranen

et al. 2019

Cancers

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Epithelial ovarian cancer (EOC) comprises multiple disease states representing a variety of distinct tumors that, irrespective of tissue of origin, genetic aberrations and pathological features, share common patterns of dissemination to the peritoneal cavity. EOC peritoneal dissemination is a stepwise process that includes the formation of malignant outgrowths that detach and establish widespread peritoneal metastases through adhesion to serosal membranes. The cell biology associated with outgrowth formation, detachment, and de novo adhesion is at the nexus of diverse genetic backgrounds that characterize the disease. Development of treatment for metastatic disease will require detailed characterization of cellular processes involved in each step of EOC peritoneal dissemination. This article offers a review of the literature that relates to the current stage of knowledge about distinct steps of EOC peritoneal dissemination, with emphasis on the cell biology aspects of the process.

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“…In this study, we have explored a possible connection between centrosome aberrations and ‘basal cell extrusion', another fundamental mechanism implicated in the dissemination of metastatic cells [ 28 , 29 ]. To the best of our knowledge, a possible connection between centrosome aberrations and basal cell extrusion has not previously been explored.…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, a possible connection between centrosome aberrations and basal cell extrusion has not previously been explored. Cell extrusion is an important process through which epithelia respond to overcrowding or cell damage [ 29 ]. In fact, the removal of aberrant cells, followed by gap closure by neighbouring healthy cells, is critical to preserve the integrity of epithelial layers [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion

Ganier¹,

Schnerch²,

Nigg³

2018

Open Biol.

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Centrosome aberrations disrupt tissue architecture and may confer invasive properties to cancer cells. Here we show that structural centrosome aberrations, induced by overexpression of either Ninein-like protein (NLP) or CEP131/AZI1, sensitize polarized mammalian epithelia to basal cell extrusion. While unperturbed epithelia typically dispose of damaged cells through apical dissemination into luminal cavities, certain oncogenic mutations cause a switch in directionality towards basal cell extrusion, raising the potential for metastatic cell dissemination. Here we report that NLP-induced centrosome aberrations trigger the preferential extrusion of damaged cells towards the basal surface of epithelial monolayers. This switch in directionality from apical to basal dissemination coincides with a profound reorganization of the microtubule cytoskeleton, which in turn prevents the contractile ring repositioning that is required to support extrusion towards the apical surface. While the basal extrusion of cells harbouring NLP-induced centrosome aberrations requires exogenously induced cell damage, structural centrosome aberrations induced by excess CEP131 trigger the spontaneous dissemination of dying cells towards the basal surface from MDCK cysts. Thus, similar to oncogenic mutations, structural centrosome aberrations can favour basal extrusion of damaged cells from polarized epithelia. Assuming that additional mutations may promote cell survival, this process could sensitize epithelia to disseminate potentially metastatic cells.

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Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

Cited by 99 publications

References 152 publications

Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm

Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm

Ovarian Cancer Dissemination—A Cell Biologist’s Perspective

Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion

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