spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online January 11, 2008
doi: 10.1242/10.1242/dev.007047

Development 135, 579-588 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, Y.
Right arrow Articles by Dean, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, Y.
Right arrow Articles by Dean, D. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Zeb1 links epithelial-mesenchymal transition and cellular senescence

Yongqing Liu1, Shahenda El-Naggar1, Douglas S. Darling2, Yujiro Higashi3 and Douglas C. Dean1,*

1 James Graham Brown Cancer Center, Department of Ophthalmology and Visual Sciences, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.
2 Departments of Peiodontics, Endodontics and Dental Hygiene, Center for Oral Health and Systemic Disease, University of Louisville School of Dentistry, Louisville, KY 40292, USA.
3 Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.

* Author for correspondence (e-mail: dcdean01{at}louisville.edu)

Accepted 16 October 2007

Overexpression of zinc finger E-box binding homeobox transcription factor 1 (Zeb1) in cancer leads to epithelial-to-mesenchymal transition (EMT) and increased metastasis. As opposed to overexpression, we show that mutation of Zeb1 in mice causes a mesenchymal-epithelial transition in gene expression characterized by ectopic expression of epithelial genes such as E-cadherin and loss of expression of mesenchymal genes such as vimentin. In contrast to rapid proliferation in cancer cells where Zeb1 is overexpressed, this mesenchymal-epithelial transition in mutant mice is associated with diminished proliferation of progenitor cells at sites of developmental defects, including the forming palate, skeleton and CNS. Zeb1 dosage-dependent deregulation of epithelial and mesenchymal genes extends to mouse embryonic fibroblasts (MEFs), and mutant MEFs also display diminished replicative capacity in culture, leading to premature senescence. Replicative senescence in MEFs is classically triggered by products of the Ink4a (Cdkn2a) gene. However, this Ink4a pathway is not activated during senescence of Zeb1 mutant MEFs. Instead, there is ectopic expression of two other cell cycle inhibitory cyclin-dependent kinase inhibitors, p15Ink4b (Cdkn2b) and p21Cdkn1a (Cdkn1a). We demonstrate that this ectopic expression of p15Ink4b extends in vivo to sites of diminished progenitor cell proliferation and developmental defects in Zeb1-null mice.

Key words: Zeb1, Epithelial-mesenchymal transition, Senescence, Transcription


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
S. El-Naggar, Y. Liu, and D. C. Dean
Mutation of the Rb1 Pathway Leads to Overexpression of mTor, Constitutive Phosphorylation of Akt on Serine 473, Resistance to Anoikis, and a Block in c-Raf Activation
Mol. Cell. Biol., November 1, 2009; 29(21): 5710 - 5717.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Y. Liu, F. Ye, Q. Li, S. Tamiya, D. S. Darling, H. J. Kaplan, and D. C. Dean
Zeb1 Represses Mitf and Regulates Pigment Synthesis, Cell Proliferation, and Epithelial Morphology
Invest. Ophthalmol. Vis. Sci., November 1, 2009; 50(11): 5080 - 5088.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. E. Sayan, T. R. Griffiths, R. Pal, G. J. Browne, A. Ruddick, T. Yagci, R. Edwards, N. J. Mayer, H. Qazi, S. Goyal, et al.
SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer
PNAS, September 1, 2009; 106(35): 14884 - 14889.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
W. Yu, L.-B. Ruest, and K. K. H. Svoboda
Regulation of Epithelial-Mesenchymal Transition in Palatal Fusion
Experimental Biology and Medicine, May 1, 2009; 234(5): 483 - 491.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Chinnadurai
The Transcriptional Corepressor CtBP: A Foe of Multiple Tumor Suppressors
Cancer Res., February 1, 2009; 69(3): 731 - 734.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. P. Bracken, P. A. Gregory, N. Kolesnikoff, A. G. Bert, J. Wang, M. F. Shannon, and G. J. Goodall
A Double-Negative Feedback Loop between ZEB1-SIP1 and the microRNA-200 Family Regulates Epithelial-Mesenchymal Transition
Cancer Res., October 1, 2008; 68(19): 7846 - 7854.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Y. Liu, X. Peng, J. Tan, D. S. Darling, H. J. Kaplan, and D. C. Dean
Zeb1 Mutant Mice as a Model of Posterior Corneal Dystrophy
Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1843 - 1849.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2008