Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells Page: 4 of 26
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developing large lamellapodia and increasing their spreading on the underlying substratum
[Radisky et al., 2005].
Modulation of cell morphology can dramatically alter cellular behaviors, such as:
glucose uptake and metabolism, [Bissell et al., 1977], cell division[Folkman and Moscona,
1978], proliferation and apoptosis[Chen et al., 1997], differentiation [Roskelley et al.,
1994; Watt et al., 1988], nuclear organization [Le Beyec et al., 2007], and morphogenesis
[Nelson et al., 2005; Nelson et al., 2006]. EMT was first defined [Greenburg and Hay,
1982] as a morphological reshaping of the epithelium that precedes mesenchymal invasion
[Kalluri and Neilson, 2003]. Culturing epithelial cells at low density can induce some
features of EMT, including a more spread morphology, downmodulation of epithelial
keratins, and upregulation of mesenchymal vimentin [Ben-Ze'ev, 1984; Maeda et al., 2005;
Sarrio et al., 2008]. Increased cell spreading is an early feature of MMP3-treated
mammary epithelial cells [Radisky et al., 2005]; we thus hypothesized that this change in
morphology might be necessary for MMP-3 to induce EMT. Here, we tested this
hypothesis in mouse mammary epithelial cells. We find that MMP-3-induced cell
spreading is required for the downstream induction of EMT. Cells treated with TGFP also
increase their spreading against the underlying substratum, but that spreading is not
required for TGFO-induced EMT. These results reveal differences between the EMT
pathways downstream of MMP-3 and TGFP, and provide insight into the causal
relationship between morphology and EMT.
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Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J. & Radisky, Derek C. Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells, article, June 26, 2008; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc901999/m1/4/: accessed October 16, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.