HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prunier, C. Articles by Atfi, A. Search for Related Content PubMed PubMed Citation Articles by Prunier, C. Articles by Atfi, A. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 33, 22919-22922, August 13, 1999

COMMUNICATION
Evidence That Smad2 Is a Tumor Suppressor Implicated in the Control of Cellular Invasion

Celine Prunier, Anne Mazars, Veerle Noë^§, Erik Bruyneel^§, Marc Mareel^§, Christian Gespach, and Azeddine Atfi

From the  INSERM U 482, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75571, Paris Cedex 12, France and the ^§ Laboratory of Experimental Cancerology, University Hospital, De Pintelaan 185, B-9000 Gent, Belgium

The Smad2 protein plays an essential role in the transforming growth factor- (TGF-) signaling pathway. This pathway mediates growth inhibitory signals from the cell surface to the nucleus. Although Smad2 protein is significantly mutated in human cancers, there is no definitive evidence implicating Smad2 as a tumor-suppressor gene. Here we show that overexpression of the tumor-derived missense mutation Smad2.D450E, an unphosphorylable form of Smad2 found in colorectal and lung cancers, did not abolish the TGF--mediated growth arrest, suggesting that resistance to the growth-inhibiting effects of TGF- exhibited by human tumors cannot be linked to the inactivation of Smad2 protein. In contrast, overexpression of Smad2.D450E induces cellular invasion, and this effect was enhanced by TGF-. A similar invasive phenotype was obtained in cells expressing another inactivating mutation in Smad2 (Smad2.P445H) found in colorectal cancer. These findings indicate that genetic defects in Smad2 are sufficient to confer the invasion-promoting effect of TGF- and reveal that TGF- acts through Smad2 to induce cellular invasion by a novel mechanism that is independent of Smad2 phosphorylation by the activated TGF- type I receptor.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. C. Wilkes, S. J. Murphy, N. Garamszegi, and E. B. Leof Cell-Type-Specific Activation of PAK2 by Transforming Growth Factor {beta} Independent of Smad2 and Smad3 Mol. Cell. Biol., December 1, 2003; 23(23): 8878 - 8889. [Abstract] [Full Text] [PDF]

				E. Dumont, F. Lallemand, C. Prunier, N. Ferrand, A. Guillouzo, B. Clement, A. Atfi, and N. Theret Evidence for a Role of Smad3 and Smad2 in Stabilization of the Tumor-derived Mutant Smad2.Q407R J. Biol. Chem., June 27, 2003; 278(27): 24881 - 24887. [Abstract] [Full Text] [PDF]

				M. Mareel and A. Leroy Clinical, Cellular, and Molecular Aspects of Cancer Invasion Physiol Rev, April 1, 2003; 83(2): 337 - 376. [Abstract] [Full Text] [PDF]

				J. Lafont, M. Laurent, H. Thibout, F. Lallemand, Y. Le Bouc, A. Atfi, and C. Martinerie The Expression of novH in Adrenocortical Cells Is Down-regulated by TGFbeta 1 through c-Jun in a Smad-independent Manner J. Biol. Chem., October 18, 2002; 277(43): 41220 - 41229. [Abstract] [Full Text] [PDF]

				K. Takaku, J. L. Wrana, E. J. Robertson, and M. M. Taketo No Effects of Smad2 (Madh2) Null Mutation on Malignant Progression of Intestinal Polyps in Apc{Delta}716 Knockout Mice Cancer Res., August 15, 2002; 62(16): 4558 - 4561. [Abstract] [Full Text] [PDF]

				M. A. Rowland-Goldsmith, H. Maruyama, T. Kusama, S. Ralli, and M. Korc Soluble Type II Transforming Growth Factor-{beta} (TGF-{beta}) Receptor Inhibits TGF-{beta} Signaling in COLO-357 Pancreatic Cancer Cells in Vitro and Attenuates Tumor Formation Clin. Cancer Res., September 1, 2001; 7(9): 2931 - 2940. [Abstract] [Full Text] [PDF]

				M. Pessah, C. Prunier, J. Marais, N. Ferrand, A. Mazars, F. Lallemand, J.-M. Gauthier, and A. Atfi c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity PNAS, May 22, 2001; 98(11): 6198 - 6203. [Abstract] [Full Text] [PDF]

				C. Prunier, N. Ferrand, B. Frottier, M. Pessah, and A. Atfi Mechanism for Mutational Inactivation of the Tumor Suppressor Smad2 Mol. Cell. Biol., May 15, 2001; 21(10): 3302 - 3313. [Abstract] [Full Text]

				S. ATTOUB, V. NOE, L. PIROLA, E. BRUYNEEL, E. CHASTRE, M. MAREEL, M. P. WYMANN, and C. GESPACH Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, Rho-, and Rac-dependent signaling pathways FASEB J, November 1, 2000; 14(14): 2329 - 2338. [Abstract] [Full Text]

				A. Mazars, F. Lallemand, C. Prunier, J. Marais, N. Ferrand, M. Pessah, G. Cherqui, and A. Atfi Evidence for a Role of the JNK Cascade in Smad7-mediated Apoptosis J. Biol. Chem., September 21, 2001; 276(39): 36797 - 36803. [Abstract] [Full Text] [PDF]