Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs

R. Grant Rowe, Xiao Yan Li, Yuexian Hu, Thomas L. Saunders, Ismo Virtanen, Antonio Garcia De Herreros, Karl Friedrich Becker, Signe Ingvarsen, Lars H. Engelholm, Guido T. Bommer, Eric R. Fearon, Stephen J. Weiss

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Epithelial - mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-fi nger transcription factor, Snail1, can trigger EMT and is suffi cient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fi brosis. Whether Snail1 also regulates the behavior of terminally differentiated mesenchymal cells remains unexplored. Using a Snai1 conditional knockout model, we now identify Snail1 as a regulator of normal mesenchymal cell function. Snail1 expression in normal fi broblasts can be induced by agonists known to promote proliferation and invasion in vivo. When challenged within a tissue-like, three-dimensional extracellular matrix, Snail1-deficient fibroblasts exhibit global alterations in gene expression, which include defects in membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive activity. Snail1-defi cient fi broblasts explanted atop the live chick chorioallantoic membrane lack tissue-invasive potential and fail to induce angiogenesis. These fi ndings establish key functions for the EMT regulator Snail1 after terminal differentiation of mesenchymal cells.

Original languageEnglish
Pages (from-to)399-408
Number of pages10
JournalJournal of Cell Biology
Volume184
Issue number3
DOIs
StatePublished - 9 Feb 2009
Externally publishedYes

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