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Article: Hippo pathway controls cell adhesion and context dependent cell competition to influence skin engraftment efficiency

TitleHippo pathway controls cell adhesion and context dependent cell competition to influence skin engraftment efficiency
Authors
KeywordsYAP1
MOB1
Fibronectin
Issue Date2019
Citation
FASEB Journal, 2019, v. 33, n. 4, p. 5548-5560 How to Cite?
Abstract© FASEB Cell competition is involved in mammalian embryogenesis and tumor elimination and progression. It was previously shown that, whereas NIH3T3 mouse fibroblasts expressing high levels of the yes-associated protein 1(YAP1) target TEA domain family (TEAD) transcription factors become “winners” in cell competitions, Madin-Darby canine kidney cells expressing activated YAP1 become “losers” and are eliminated from culture monolayers. Thus, YAP1’s role in cell competitions is clearly context dependent. Here, we show that keratinocytes overexpressing a constitutively activated YAP1 mutant lose in in vitro competitions with control cells conducted in standard tissue culture dishes and undergo apical extrusion. Similarly, cells in which endogenous YAP1 is activated by NF2 knockdown become losers. The YAP1-overexpressing cells exhibit a decrease in cell-matrix adhesion because of defective expression of adhesion molecules such as fibronectin-1. Cell adhesion–mediated proliferation is also impaired. However, because of intrinsic factors, YAP1-expressing cells proliferate faster than control cells when cocultured in dishes impeding cell adhesion. In vivo, Mob1a/b-deficient (YAP1-activated) epidermis, which shows decreased expression of type XVII collagen, cannot be engrafted successfully onto donor mice. YAP1-activated skin grafts shrink away from surrounding control skin, and the epidermis peels off the basement membrane. Our data show that YAP1 activation controls cell competition in part by decreasing cell adhesion.
Persistent Identifierhttp://hdl.handle.net/10722/292108
ISSN
2023 Impact Factor: 4.4
2023 SCImago Journal Rankings: 1.412
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNishio, Miki-
dc.contributor.authorMiyachi, Yousuke-
dc.contributor.authorOtani, Junji-
dc.contributor.authorTane, Shoji-
dc.contributor.authorOmori, Hirofumi-
dc.contributor.authorUeda, Fumihito-
dc.contributor.authorTogashi, Hideru-
dc.contributor.authorSasaki, Takehiko-
dc.contributor.authorMak, Tak Wah-
dc.contributor.authorNakao, Kazuwa-
dc.contributor.authorFujita, Yasuyuki-
dc.contributor.authorNishina, Hiroshi-
dc.contributor.authorMaehama, Tomohiko-
dc.contributor.authorSuzuki, Akira-
dc.date.accessioned2020-11-17T14:55:47Z-
dc.date.available2020-11-17T14:55:47Z-
dc.date.issued2019-
dc.identifier.citationFASEB Journal, 2019, v. 33, n. 4, p. 5548-5560-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/292108-
dc.description.abstract© FASEB Cell competition is involved in mammalian embryogenesis and tumor elimination and progression. It was previously shown that, whereas NIH3T3 mouse fibroblasts expressing high levels of the yes-associated protein 1(YAP1) target TEA domain family (TEAD) transcription factors become “winners” in cell competitions, Madin-Darby canine kidney cells expressing activated YAP1 become “losers” and are eliminated from culture monolayers. Thus, YAP1’s role in cell competitions is clearly context dependent. Here, we show that keratinocytes overexpressing a constitutively activated YAP1 mutant lose in in vitro competitions with control cells conducted in standard tissue culture dishes and undergo apical extrusion. Similarly, cells in which endogenous YAP1 is activated by NF2 knockdown become losers. The YAP1-overexpressing cells exhibit a decrease in cell-matrix adhesion because of defective expression of adhesion molecules such as fibronectin-1. Cell adhesion–mediated proliferation is also impaired. However, because of intrinsic factors, YAP1-expressing cells proliferate faster than control cells when cocultured in dishes impeding cell adhesion. In vivo, Mob1a/b-deficient (YAP1-activated) epidermis, which shows decreased expression of type XVII collagen, cannot be engrafted successfully onto donor mice. YAP1-activated skin grafts shrink away from surrounding control skin, and the epidermis peels off the basement membrane. Our data show that YAP1 activation controls cell competition in part by decreasing cell adhesion.-
dc.languageeng-
dc.relation.ispartofFASEB Journal-
dc.subjectYAP1-
dc.subjectMOB1-
dc.subjectFibronectin-
dc.titleHippo pathway controls cell adhesion and context dependent cell competition to influence skin engraftment efficiency-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1096/fj.201802005R-
dc.identifier.pmid30640535-
dc.identifier.scopuseid_2-s2.0-85064132249-
dc.identifier.volume33-
dc.identifier.issue4-
dc.identifier.spage5548-
dc.identifier.epage5560-
dc.identifier.eissn1530-6860-
dc.identifier.isiWOS:000462888500073-
dc.identifier.issnl0892-6638-

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