Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print February 2, 2005
Mol. Biol. Cell 10.1091/mbc.E04-08-0658

A more recent version of this article appeared on April 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E04-08-0658v1
16/4/1987    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Valcourt, U.
Right arrow Articles by Moustakas, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Valcourt, U.
Right arrow Articles by Moustakas, A.

Submitted on August 3, 2004
Accepted on January 21, 2005

TGF-{beta} and the Smad Signaling Pathway Support Transcriptomic Reprogramming during Epithelial-Mesenchymal Cell Transition

Ulrich Valcourt,*{dagger} Marcin Kowanetz,* Hideki Niimi, Carl-Henrik Heldin, and Aristidis Moustakas

Ludwig Institute for Cancer Research, SE-751 24 Uppsala, Sweden

Monitoring Editor: Keith Yamamoto

Epithelial-mesenchymal transition (EMT) contributes to normal tissue patterning and carcinoma invasiveness. We show that transforming growth factor (TGF)-{beta}/activin members, but not bone morphogenetic protein (BMP) members, can induce EMT in normal human and mouse epithelial cells. EMT correlates with the ability of these ligands to induce growth arrest. Ectopic expression of all type I receptors of the TGF-{beta} superfamily establishes that TGF-{beta} but not BMP pathways can elicit EMT. Ectopic Smad2 or Smad3 together with Smad4 enhanced, while dominant-negative forms of Smad2, Smad3 or Smad4, and wild-type inhibitory Smad7, blocked TGF-{beta}-induced EMT. Transcriptomic analysis of EMT kinetics identified novel TGF-{beta} target genes with ligand-specific responses. Using a TGF-{beta} type I receptor that cannot activate Smads nor induce EMT, we found that Smad signaling is critical for regulation of all tested gene targets during EMT. One such gene, Id2, whose expression is repressed by TGF-{beta}1 but induced by BMP-7 is critical for regulation of at least one important myoepithelial marker, {alpha}-smooth muscle actin, during EMT. Thus, based on ligand-specific responsiveness and evolutionary conservation of the gene expression patterns, we begin deciphering a genetic network downstream of TGF-{beta} and predict functional links to the control of cell proliferation and EMT.

*These authors contributed equally to this work.

{dagger}Present address: INSERM Unit 403, Hopital E. Herriot, Pavillon F, 69437 Lyon Cedex 03, France.

Address correspondence to: Aristidis Moustakas (aris.moustakas{at}licr.uu.se)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2005 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.