Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells Page: 7 of 26
This article is part of the collection entitled: Office of Scientific & Technical Information Technical Reports and was provided to Digital Library by the UNT Libraries Government Documents Department.
The following text was automatically extracted from the image on this page using optical character recognition software:
The tumors that arise as the result of inappropriate MMP3 expression in mammary
glands of transgenic mice exhibit EMT [Sternlicht et al., 1999]. We showed that treatment
with MMP3 is directly responsible for induction of EMT in mouse cells in culture
[Lochter et al., 1997a; Lochter et al., 1997b; Radisky et al., 2005]. The MMP3-induced
EMT is characterized by cell scattering, down-regulation of epithelial markers such as
cytokeratins and E-cadherin, and up-regulation of mesenchymal markers including
vimentin, a-smooth muscle actin, and the transcription factor Snail [Radisky et al., 2005].
Additionally, MMP3-induced EMT is accompanied by altered cellular morphology, with
loss of colonial morphology, increased lamellipodia (Figure la), and substantial increase
in cell spreading (as measured by projected cell area) against the underlying substratum
(Figure ib). The catalytic activity of MMP3 is required for increased cell spreading and
EMT since both are blocked by treatment with the broad spectrum MMP inhibitor,
We previously showed that MMP3 induces EMT through a cascade involving the
generation of Raclb, a highly active splice variant of Racl [Radisky et al., 2005]. We now
find that MMP3-induced cell spreading is a consequence of the induction of Raclb.
Exogenous expression of Raclb induces cell scattering (Figure 2a), increases expression
of EMT markers such as a-smooth muscle actin (Figure 2b) and increases cell spreading
(Figure 2c); knockdown of Raclb by siRNA blocks both MMP-3-induced expression of
a-smooth muscle actin (Figure 2d) and cell spreading (Figure 2e). Our previous studies
showed that Raclb led to the production of cellular reactive oxygen species (ROS), which
led to upregulation of the EMT-inducing transcription factor, Snail [Radisky et al., 2005].
Here’s what’s next.
This article can be searched. Note: Results may vary based on the legibility of text within the document.
Tools / Downloads
Get a copy of this page or view the extracted text.
Citing and Sharing
Basic information for referencing this web page. We also provide extended guidance on usage rights, references, copying or embedding.
Reference the current page of this Article.
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. (https://digital.library.unt.edu/ark:/67531/metadc901999/m1/7/: accessed April 25, 2019), University of North Texas Libraries, Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.