Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs
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Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs. / Rowe, R.G.; Li, X.Y.; Hu, Y.; Saunders, T.L.; Virtanen, I.; A., Garcia de Herreros; Becker, K.F.; Ingvarsen, S.; Engelholm, L.H.; Bommer, G.T.; Fearon, E.R.; Weiss, S.J.
In: Journal of Cell Biology, Vol. 184, No. 3, 2009, p. 399-408.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs
AU - Rowe, R.G.
AU - Li, X.Y.
AU - Hu, Y.
AU - Saunders, T.L.
AU - Virtanen, I.
AU - A., Garcia de Herreros
AU - Becker, K.F.
AU - Ingvarsen, S.
AU - Engelholm, L.H.
AU - Bommer, G.T.
AU - Fearon, E.R.
AU - Weiss, S.J.
PY - 2009
Y1 - 2009
N2 - Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. 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 fibroblasts 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-deficient fibroblasts explanted atop the live chick chorioallantoic membrane lack tissue-invasive potential and fail to induce angiogenesis. These findings establish key functions for the EMT regulator Snail1 after terminal differentiation of mesenchymal cells Udgivelsesdato: 2009/2/9
AB - Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. 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 fibroblasts 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-deficient fibroblasts explanted atop the live chick chorioallantoic membrane lack tissue-invasive potential and fail to induce angiogenesis. These findings establish key functions for the EMT regulator Snail1 after terminal differentiation of mesenchymal cells Udgivelsesdato: 2009/2/9
M3 - Journal article
VL - 184
SP - 399
EP - 408
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 3
ER -
ID: 19600122