Skip Navigation


Carcinogenesis Advance Access originally published online on February 1, 2007
Carcinogenesis 2007 28(6):1153-1162; doi:10.1093/carcin/bgm015
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
28/6/1153    most recent
bgm015v1
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 ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (10)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Thériault, B. L.
Right arrow Articles by Nachtigal, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thériault, B. L.
Right arrow Articles by Nachtigal, M. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

BMP4 induces EMT and Rho GTPase activation in human ovarian cancer cells

Brigitte L. Thériault, Trevor G. Shepherd, Michelle L. Mujoomdar and Mark W. Nachtigal*

Department of Pharmacology, Faculty of Medicine, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5

* To whom correspondence should be addressed. Tel: +902 494 6348; Fax: +902 494 1388; Email: mark.nachtigal{at}dal.ca

We identified previously an autocrine bone morphogenetic protein-4 (BMP4) signalling pathway in primary human normal ovarian surface epithelial (OSE) and epithelial ovarian cancer (OvCa) cells. Herein we show that treatment of OvCa cells with BMP4 produced morphological alterations and increased cellular adhesion, motility and invasion. The BMP4 inhibitor noggin blocked the BMP4-induced phenotype, and decreased autocrine BMP4-mediated OvCa cell motility and adherence. In response to exogenous BMP4, the epithelial–mesenchymal transition (EMT) markers Snail and Slug mRNA and protein were up-regulated, E-cadherin mRNA and protein were down-regulated and the network of alpha smooth muscle actin changed to resemble a mesenchymal cell. We also observed changes in the level of activated Rho GTPases in OvCa cells treated with BMP4, strongly suggesting that the changes in morphology, adhesion, motility and invasion are probably mediated through the activation of these molecules. Strikingly, treatment of normal OSE cells with BMP4 or noggin failed to alter cell motility, providing evidence that OSE and OvCa cells possess a distinct capability to respond to BMP4. Overall, our studies suggest a link between autocrine BMP signalling mediated through the Rho GTPase family and Snail- and Slug-induced EMT that may collectively contribute to aggressive OvCa behaviour.

Abbreviations: BMP, bone morphogenetic protein; BSA, bovine serum albumin; EMT, epithelial–mesenchymal transition; FAP, focal adhesion protein; FBS, fetal bovine serum; LIMK1, LIM Kinase 1; NT, non-transduced; OSE, ovarian surface epithelial; OvCa, ovarian cancer; PBS, phosphate-buffered saline; QPCR, quantitative polymerase chain reaction; RT, room temperature

Received October 2, 2006; revised January 12, 2007; accepted January 15, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
Y. Liu, W. Ren, R. Warburton, D. Toksoz, and B. L. Fanburg
Serotonin induces Rho/ROCK-dependent activation of Smads 1/5/8 in pulmonary artery smooth muscle cells
FASEB J, July 1, 2009; 23(7): 2299 - 2306.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
V. Fendrich, J. Waldmann, G. Feldmann, K. Schlosser, A. Konig, A. Ramaswamy, D. K Bartsch, and E. Karakas
Unique expression pattern of the EMT markers Snail, Twist and E-cadherin in benign and malignant parathyroid neoplasia
Eur. J. Endocrinol., April 1, 2009; 160(4): 695 - 703.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
K. J. Gordon, K. C. Kirkbride, T. How, and G. C. Blobe
Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2
Carcinogenesis, February 1, 2009; 30(2): 238 - 248.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. L. Pon, H. Y. Zhou, A. N.Y. Cheung, H. Y.S. Ngan, and A. S.T. Wong
p70 S6 Kinase Promotes Epithelial to Mesenchymal Transition through Snail Induction in Ovarian Cancer Cells
Cancer Res., August 15, 2008; 68(16): 6524 - 6532.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
N. Kinoshita, N. Sasai, K. Misaki, and S. Yonemura
Apical Accumulation of Rho in the Neural Plate Is Important for Neural Plate Cell Shape Change and Neural Tube Formation
Mol. Biol. Cell, May 1, 2008; 19(5): 2289 - 2299.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. C. Kirkbride, T. A. Townsend, M. W. Bruinsma, J. V. Barnett, and G. C. Blobe
Bone Morphogenetic Proteins Signal through the Transforming Growth Factor-{beta} Type III Receptor
J. Biol. Chem., March 21, 2008; 283(12): 7628 - 7637.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.