Snail induces epithelial cell extrusion by regulating RhoA contractile signalling and cell–matrix adhesion

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dc.contributor.authorWee, K.
dc.contributor.authorHediyeh-Zadeh, S.
dc.contributor.authorDuszyc, K.
dc.contributor.authorVerma, S.
dc.contributor.authorNanavati, B.N.
dc.contributor.authorKhare, S.
dc.contributor.authorVarma, A.
dc.contributor.authorDaly, R.J.
dc.contributor.authorYap, A.S.
dc.contributor.authorDavis, M.J.
dc.contributor.authorBudnar, S.
dc.date.issued2020
dc.description.abstractCell extrusion is a morphogenetic process that is implicated in epithelial homeostasis and elicited by stimuli ranging from apoptosis to oncogenic transformation. To explore whether the morphogenetic transcription factor Snail (SNAI1) induces extrusion, we inducibly expressed a stabilized Snail6SA transgene in confluent MCF-7 monolayers. When expressed in small clusters (less than three cells) within otherwise wild-type confluent monolayers, Snail6SA expression induced apical cell extrusion. In contrast, larger clusters or homogenous cultures of Snail6SA cells did not show enhanced apical extrusion, but eventually displayed sporadic basal delamination. Transcriptomic profiling revealed that Snail6SA did not substantively alter the balance of epithelial and mesenchymal genes. However, we identified a transcriptional network that led to upregulated RhoA signalling and cortical contractility in cells expressing Snail6SA. Enhanced contractility was necessary, but not sufficient, to drive extrusion, suggesting that Snail collaborates with other factors. Indeed, we found that the transcriptional downregulation of cell–matrix adhesion cooperates with contractility to mediate basal delamination. This provides a pathway for Snail to influence epithelial morphogenesis independently of classic epithelial-to-mesenchymal transition.
dc.description.statementofresponsibilityKenneth Wee, Soroor Hediyeh-zadeh, Kinga Duszyc, Suzie Verma, Bageshri N. Nanavati, Satyajeet Khare, Amrita Varma, Roger J. Daly, Alpha S. Yap, Melissa J. Davis, and Srikanth Budnar
dc.identifier.citationJournal of Cell Science, 2020; 133(13):1-12
dc.identifier.doi10.1242/jcs.235622
dc.identifier.issn0021-9533
dc.identifier.issn1477-9137
dc.identifier.orcidDavis, M.J. [0000-0003-4864-7033]
dc.identifier.urihttps://hdl.handle.net/2440/134984
dc.language.isoen
dc.publisherThe Company of Biologists
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1058540
dc.relation.granthttp://purl.org/au-research/grants/arc/CE140100036
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1044041
dc.rights© 2020. Published by The Company of Biologists Ltd
dc.source.urihttps://doi.org/10.1242/jcs.235622
dc.subjectSnail; RhoA; Contractility; Extrusion; ECM; Adhesion; Delamination
dc.subject.meshCell-Matrix Junctions
dc.subject.meshEpithelial Cells
dc.subject.meshTranscription Factors
dc.subject.meshSignal Transduction
dc.subject.meshEpithelial-Mesenchymal Transition
dc.subject.meshSnail Family Transcription Factors
dc.titleSnail induces epithelial cell extrusion by regulating RhoA contractile signalling and cell–matrix adhesion
dc.typeJournal article
pubs.publication-statusPublished

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