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dc.contributor.authorGómez-Escudero, Jesús
dc.contributor.authorMoreno, Vanessa
dc.contributor.authorMartín-Alonso, Mara
dc.contributor.authorHernández de Riquer, M. Victoria
dc.contributor.authorFeinberg, Tamar
dc.contributor.authorColmenar, Ángel
dc.contributor.authorCalvo, Enrique
dc.contributor.authorCamafeita, Emilio
dc.contributor.authorMartínez, Fernando
dc.contributor.authorJ. Weiss, Stephen
dc.contributor.authorArroyo, Alicia G.
dc.contributor.authorJ. Oudhoff, Menno
dc.date.accessioned2018-01-04T12:18:45Z
dc.date.available2018-01-04T12:18:45Z
dc.date.created2018-01-02T12:12:16Z
dc.date.issued2017
dc.identifier.issn0021-9533
dc.identifier.urihttp://hdl.handle.net/11250/2475666
dc.description.abstractCadherin-based intercellular adhesions are essential players in epithelial homeostasis, but their dynamic regulation during tissue morphogenesis and remodeling remain largely undefined. Herein, we characterize an unexpected role for the membrane-anchored metalloproteinase MT2-MMP in regulating epithelial cell quiescence. Following coimmunoprecipitation and mass spectrometry, the MT2-MMP cytosolic tail was found to interact with the zonula occludens protein-1 (ZO-1) at the apical junctions of polarized epithelial cells. Functionally, MT2-MMP localizes in the apical domain of epithelial cells where it cleaves E-cadherin and promotes epithelial cell accumulation, a phenotype observed in 2D polarized cells as well as 3D cysts. MT2-MMP-mediated cleavage subsequently disrupts apical E-cadherin-mediated cell quiescence resulting in; i) relaxed apical cortical tension favoring cell extrusion and ii) re-sorting of Src kinase activity to junctional complexes, thereby promoting proliferation. Physiologically, MT2-MMP lossof- function alters E-cadherin distribution leading to impaired 3D organoid formation by mouse colonic epithelial cells ex vivo and reduction of cell proliferation within intestinal crypts in vivo. Taken together, these studies identify an MT2-MMP/E-cadherin axis that functions as a novel regulator of epithelial cell homeostasis in vivo.nb_NO
dc.language.isoengnb_NO
dc.publisherCompany of Biologistsnb_NO
dc.titleE-cadherin cleavage by MT2-MMP regulates apical junctional signaling and epithelial homeostasis in the intestinenb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber4013-4027nb_NO
dc.source.volume130nb_NO
dc.source.journalJournal of Cell Sciencenb_NO
dc.identifier.doi10.1242/jcs.203687
dc.identifier.cristin1533666
dc.description.localcode© 2017. Published by The Company of Biologists Ltd. Locked until 13.10.2018 due to copyright restrictions.nb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextpreprint
cristin.qualitycode2


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