Cancer Research Audrey Hepburn  Jordan
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

Cancer Research 67, 6981, July 15, 2007. doi: 10.1158/0008-5472.CAN-07-0491
© 2007 American Association for Cancer Research

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Dennler, S.
Right arrow Articles by Mauviel, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dennler, S.
Right arrow Articles by Mauviel, A.

Experimental Therapeutics, Molecular Targets, and Chemical Biology

Induction of Sonic Hedgehog Mediators by Transforming Growth Factor-ß: Smad3-Dependent Activation of Gli2 and Gli1 Expression In vitro and In vivo

Sylviane Dennler1, Jocelyne André1, Ismini Alexaki1, Allen Li2, Thierry Magnaldo3, Peter ten Dijke4, Xiao-Jing Wang2, Franck Verrecchia1 and Alain Mauviel1

1 Institut National de la Sante et de la Recherche Medicale U697, Paris, France; 2 Department of Otolaryngology, Oregon Health and Science University, Portland, Oregon; 3 Centre National de la Recherche Scientifique UPR 2169, Institut Gustave-Roussy, Villejuif, France; and 4 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands

Requests for reprints: Alain Mauviel, Institut National de la Sante et de la Recherche Medicale U697, Hôpital Saint-Louis, Pavillon Bazin, 1, Avenue Claude Vellefaux, 75010 Paris, France. Phone: 33-1-53-72-20-69; Fax: 33-1-53-72-20-51; E-mail: alain.mauviel{at}stlouis.inserm.fr.

Hedgehog (Hh) and transforming growth factor-ß (TGF-ß) family members are involved in numerous overlapping processes during embryonic development, hair cycle, and cancer. Herein, we show that TGF-ß induces the expression of the Hh signaling molecules Gli1 and Gli2 in various human cell types, including normal fibroblasts and keratinocytes, as well as various cancer cell lines. Gli2 induction by TGF-ß is rapid, independent from Hh receptor signaling, and requires a functional Smad pathway. Gli1 expression is subsequently activated in a Gli2-dependent manner. In transgenic mice overexpressing TGF-ß1 in the skin, Gli1 and Gli2 expression is also elevated and depends on Smad3. In pancreatic adenocarcinoma cell lines resistant to Hh inhibition, pharmacologic blockade of TGF-ß signaling leads to repression of cell proliferation accompanied with a reduction in Gli2 expression. We thus identify TGF-ß as a potent transcriptional inducer of Gli transcription factors. Targeting the cooperation of Hh and TGF-ß signaling may provide new therapeutic opportunities for cancer treatment. [Cancer Res 2007;67(14):6981–6]




This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
S. Dennler, J. Andre, F. Verrecchia, and A. Mauviel
Cloning of the Human GLI2 Promoter: TRANSCRIPTIONAL ACTIVATION BY TRANSFORMING GROWTH FACTOR-{beta} VIA SMAD3/{beta}-CATENIN COOPERATION
J. Biol. Chem., November 13, 2009; 284(46): 31523 - 31531.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. M. Hyman, A. J. Firestone, V. M. Heine, Y. Zhao, C. A. Ocasio, K. Han, M. Sun, P. G. Rack, S. Sinha, J. J. Wu, et al.
Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade
PNAS, August 18, 2009; 106(33): 14132 - 14137.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
O. Dakhova, M. Ozen, C. J. Creighton, R. Li, G. Ayala, D. Rowley, and M. Ittmann
Global Gene Expression Analysis of Reactive Stroma in Prostate Cancer
Clin. Cancer Res., June 15, 2009; 15(12): 3979 - 3989.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Beauchamp, G. Bulut, O. Abaan, K. Chen, A. Merchant, W. Matsui, Y. Endo, J. S. Rubin, J. Toretsky, and A. Uren
GLI1 Is a Direct Transcriptional Target of EWS-FLI1 Oncoprotein
J. Biol. Chem., April 3, 2009; 284(14): 9074 - 9082.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
R. Soleti, T. Benameur, C. Porro, M. A. Panaro, R. Andriantsitohaina, and M. C. Martinez
Microparticles harboring Sonic Hedgehog promote angiogenesis through the upregulation of adhesion proteins and proangiogenic factors
Carcinogenesis, April 1, 2009; 30(4): 580 - 588.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
O. Nolan-Stevaux, J. Lau, M. L. Truitt, G. C. Chu, M. Hebrok, M. E. Fernandez-Zapico, and D. Hanahan
GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation
Genes & Dev., January 1, 2009; 23(1): 24 - 36.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. Li, C. Li, Y.-h. Liu, Y. Xing, L. Hu, Z. Borok, K. Y.-C. Kwong, and P. Minoo
Mesodermal Deletion of Transforming Growth Factor-{beta} Receptor II Disrupts Lung Epithelial Morphogenesis: CROSS-TALK BETWEEN TGF-{beta} AND SONIC HEDGEHOG PATHWAYS
J. Biol. Chem., December 26, 2008; 283(52): 36257 - 36264.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
G. V. Hegde, C. M. Munger, K. Emanuel, A. D. Joshi, T. C. Greiner, D. D. Weisenburger, J. M. Vose, and S. S. Joshi
Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma
Mol. Cancer Ther., June 1, 2008; 7(6): 1450 - 1460.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
R. W. Padgett and M. Reiss
TGF{beta} superfamily signaling: notes from the desert
Development, October 15, 2007; 134(20): 3565 - 3569.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.