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https://hdl.handle.net/2440/134984
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Type: | Journal article |
Title: | Snail induces epithelial cell extrusion by regulating RhoA contractile signalling and cell–matrix adhesion |
Author: | Wee, K. Hediyeh-Zadeh, S. Duszyc, K. Verma, S. Nanavati, B.N. Khare, S. Varma, A. Daly, R.J. Yap, A.S. Davis, M.J. Budnar, S. |
Citation: | Journal of Cell Science, 2020; 133(13):1-12 |
Publisher: | The Company of Biologists |
Issue Date: | 2020 |
ISSN: | 0021-9533 1477-9137 |
Statement of Responsibility: | Kenneth 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 |
Abstract: | Cell 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. |
Keywords: | Snail; RhoA; Contractility; Extrusion; ECM; Adhesion; Delamination |
Rights: | © 2020. Published by The Company of Biologists Ltd |
DOI: | 10.1242/jcs.235622 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1058540 http://purl.org/au-research/grants/arc/CE140100036 http://purl.org/au-research/grants/nhmrc/1044041 |
Published version: | http://dx.doi.org/10.1242/jcs.235622 |
Appears in Collections: | Molecular and Biomedical Science publications |
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