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

Journal of cell science (2020-05-30)
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, 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.

MATERIALS
Product Number
Brand
Product Description

Roche
Anti-GFP, from mouse IgG1κ (clones 7.1 and 13.1)
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Anti-Myosin IIA, non muscle antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
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Anti-Partitioning-defective 3 Antibody, Upstate®, from rabbit
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Anti-ECT2 Antibody, from rabbit, purified by affinity chromatography