© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 17, 1388-1402,
September 6, 2000
© 2000 Oxford University Press
REVIEW |
Role of Transforming Growth Factor-ß Signaling in Cancer
Affiliation of authors: Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
Correspondence to: Anita B. Roberts, Ph.D., National Institutes of Health, Bldg. 41, Rm. C629, 41 Library Drive, MSC 5055, Bethesda, MD 20892-5055 (e-mail: (Robertsa{at}dce41.nci.nih.gov).
Signaling from transforming growth factor-ß (TGF-ß) through its unique transmembrane receptor serine–threonine kinases plays a complex role in carcinogenesis, having both tumor suppressor and oncogenic activities. Tumor cells often escape from the antiproliferative effects of TGF-ß by mutational inactivation or dysregulated expression of components in its signaling pathway. Decreased receptor function and altered ratios of the TGF-ß type I and type II receptors found in many tumor cells compromise the tumor suppressor activities of TGF-ß and enable its oncogenic functions. Recent identification of a family of intracellular mediators, the Smads, has provided new paradigms for understanding mechanisms of subversion of TGF-ß signaling by tumor cells. In addition, several proteins recently have been identified that can modulate the Smad-signaling pathway and may also be targets for mutation in cancer. Other pathways such as various mitogen-activated protein kinase cascades also contribute substantially to TGF-ß signaling. Understanding the interplay between these signaling cascades as well as the complex patterns of cross-talk with other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional tumor suppressor/oncogene role of TGF-ß in carcinogenesis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. V. Miller, S. E. Alvarez, S. Spiegel, and D. A. Lebman Sphingosine Kinases and Sphingosine-1-Phosphate Are Critical for Transforming Growth Factor {beta}-Induced Extracellular Signal-Regulated Kinase 1 and 2 Activation and Promotion of Migration and Invasion of Esophageal Cancer Cells Mol. Cell. Biol., June 15, 2008; 28(12): 4142 - 4151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Biasi, C. Mascia, and G. Poli The contribution of animal fat oxidation products to colon carcinogenesis, through modulation of TGF-{beta}1 signaling Carcinogenesis, May 1, 2008; 29(5): 890 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Kim, J. H. Kwak, L. Wang, and M. E. Choi Protein Phosphatase 2A Is a Negative Regulator of Transforming Growth Factor-{beta}1-induced TAK1 Activation in Mesangial Cells J. Biol. Chem., April 18, 2008; 283(16): 10753 - 10763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kotzsch, J. Nickel, A. Seher, K. Heinecke, L. van Geersdaele, T. Herrmann, W. Sebald, and T. D. Mueller Structure Analysis of Bone Morphogenetic Protein-2 Type I Receptor Complexes Reveals a Mechanism of Receptor Inactivation in Juvenile Polyposis Syndrome J. Biol. Chem., February 29, 2008; 283(9): 5876 - 5887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Lee, U. S. Kayyali, A. M. Sousa, T. Rajan, R. J. Lechleider, and R. M. Day Transforming Growth Factor-beta1 Effects on Endothelial Monolayer Permeability Involve Focal Adhesion Kinase/Src Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 485 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-H. Lee, W. Chen, S. Stippec, and M. H. Cobb Biological Cross-talk between WNK1 and the Transforming Growth Factor beta-Smad Signaling Pathway J. Biol. Chem., June 22, 2007; 282(25): 17985 - 17996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Daibata, Y. Nemoto, K. Bandobashi, N. Kotani, M. Kuroda, M. Tsuchiya, H. Okuda, T. Takakuwa, S. Imai, T. Shuin, et al. Promoter Hypermethylation of the Bone Morphogenetic Protein-6 Gene in Malignant Lymphoma Clin. Cancer Res., June 15, 2007; 13(12): 3528 - 3535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sekimoto, K. Matsuzaki, K. Yoshida, S. Mori, M. Murata, T. Seki, H. Matsui, J.-i. Fujisawa, and K. Okazaki Reversible Smad-Dependent Signaling between Tumor Suppression and Oncogenesis Cancer Res., June 1, 2007; 67(11): 5090 - 5096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Buck, M. Buchholz, M. Wagner, G. Adler, T. Gress, and V. Ellenrieder The Tumor Suppressor KLF11 Mediates a Novel Mechanism in Transforming Growth Factor {beta}-Induced Growth Inhibition That Is Inactivated in Pancreatic Cancer Mol. Cancer Res., November 1, 2006; 4(11): 861 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Liby, M. Rendi, N. Suh, D. B. Royce, R. Risingsong, C. R. Williams, W. Lamph, F. Labrie, S. Krajewski, X. Xu, et al. The Combination of the Rexinoid, LG100268, and a Selective Estrogen Receptor Modulator, Either Arzoxifene or Acolbifene, Synergizes in the Prevention and Treatment of Mammary Tumors in an Estrogen Receptor-Negative Model of Breast Cancer. Clin. Cancer Res., October 1, 2006; 12(19): 5902 - 5909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Cat, D. Stuhlmann, H. Steinbrenner, L. Alili, O. Holtkotter, H. Sies, and P. Brenneisen Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species J. Cell Sci., July 1, 2006; 119(13): 2727 - 2738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Pyatt, R. Pilarski, and T. W. Prior Mutation Screening in Juvenile Polyposis Syndrome J. Mol. Diagn., February 1, 2006; 8(1): 84 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Preynat-Seauve, P. Schuler, E. Contassot, F. Beermann, B. Huard, and L. E. French Tumor-Infiltrating Dendritic Cells Are Potent Antigen-Presenting Cells Able to Activate T Cells and Mediate Tumor Rejection J. Immunol., January 1, 2006; 176(1): 61 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ohgushi, S. Kuroki, H. Fukamachi, L. A. O'Reilly, K. Kuida, A. Strasser, and S. Yonehara Transforming Growth Factor {beta}-Dependent Sequential Activation of Smad, Bim, and Caspase-9 Mediates Physiological Apoptosis in Gastric Epithelial Cells Mol. Cell. Biol., November 15, 2005; 25(22): 10017 - 10028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Jin, B.-C. Kim, C. Tognon, H.-J. Lee, S. Patel, C. L. Lannon, J. M. Maris, T. J. Triche, P. H. B. Sorensen, and S.-J. Kim The ETV6-NTRK3 chimeric tyrosine kinase suppresses TGF-{beta} signaling by inactivating the TGF-{beta} type II receptor PNAS, November 8, 2005; 102(45): 16239 - 16244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Grady Transforming Growth Factor-{beta}, Smads, and Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3151 - 3154. [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Kim, L. Luo, S. C. Pflugfelder, and D.-Q. Li Doxycycline Inhibits TGF-{beta}1-Induced MMP-9 via Smad and MAPK Pathways in Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 840 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Maeda, K. R. Johnson, and M. J. Wheelock Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition J. Cell Sci., March 1, 2005; 118(5): 873 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Kamaraju and A. B. Roberts Role of Rho/ROCK and p38 MAP Kinase Pathways in Transforming Growth Factor-{beta}-mediated Smad-dependent Growth Inhibition of Human Breast Carcinoma Cells in Vivo J. Biol. Chem., January 14, 2005; 280(2): 1024 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamagata, K. Matsuzaki, S. Mori, K. Yoshida, Y. Tahashi, F. Furukawa, G. Sekimoto, T. Watanabe, Y. Uemura, N. Sakaida, et al. Acceleration of Smad2 and Smad3 Phosphorylation via c-Jun NH2-Terminal Kinase during Human Colorectal Carcinogenesis Cancer Res., January 1, 2005; 65(1): 157 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.S. Prime, M. Pring, M. Davies, and I.C. Paterson TGF-{beta} SIGNAL TRANSDUCTION IN ORO-FACIAL HEALTH AND NON-MALIGNANT DISEASE (PART I) Crit. Rev. Oral. Biol. Med., November 1, 2004; 15(6): 324 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.S. Prime, M. Davies, M. Pring, and I.C. Paterson THE ROLE OF TGF-{beta} IN EPITHELIAL MALIGNANCY AND ITS RELEVANCE TO THE PATHOGENESIS OF ORAL CANCER (PART II) Crit. Rev. Oral. Biol. Med., November 1, 2004; 15(6): 337 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashida and H. W. Schnaper High Ambient Glucose Enhances Sensitivity to TGF-{beta}1 via Extracellular Signal--Regulated Kinase and Protein Kinase C{delta} Activities in Human Mesangial Cells J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2032 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tian, S. D. Byfield, W. T. Parks, C. H. Stuelten, D. Nemani, Y. E. Zhang, and A. B. Roberts Smad-Binding Defective Mutant of Transforming Growth Factor {beta} Type I Receptor Enhances Tumorigenesis but Suppresses Metastasis of Breast Cancer Cell Lines Cancer Res., July 1, 2004; 64(13): 4523 - 4530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Frederick, N. T. Liberati, D. S. Waddell, Y. Shi, and X.-F. Wang Transforming Growth Factor {beta}-Mediated Transcriptional Repression of c-myc Is Dependent on Direct Binding of Smad3 to a Novel Repressive Smad Binding Element Mol. Cell. Biol., March 15, 2004; 24(6): 2546 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sowa, H. Kaji, R. Kitazawa, S. Kitazawa, T. Tsukamoto, S. Yano, T. Tsukada, L. Canaff, G. N. Hendy, T. Sugimoto, et al. Menin Inactivation Leads to Loss of Transforming Growth Factor {beta} Inhibition of Parathyroid Cell Proliferation and Parathyroid Hormone Secretion Cancer Res., March 15, 2004; 64(6): 2222 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lewis, E. Burstein, S. B. Reffey, S. B. Bratton, A. B. Roberts, and C. S. Duckett Uncoupling of the Signaling and Caspase-inhibitory Properties of X-linked Inhibitor of Apoptosis J. Biol. Chem., March 5, 2004; 279(10): 9023 - 9029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-h. Cheng, J. F. Ponte, and S. Thiagalingam Elucidation of Epigenetic Inactivation of SMAD8 in Cancer Using Targeted Expressed Gene Display Cancer Res., March 1, 2004; 64(5): 1639 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. DaCosta Byfield, C. Major, N. J. Laping, and A. B. Roberts SB-505124 Is a Selective Inhibitor of Transforming Growth Factor-{beta} Type I Receptors ALK4, ALK5, and ALK7 Mol. Pharmacol., March 1, 2004; 65(3): 744 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Kim, H.-S. Jong, T.-Y. Kim, J. W. Lee, N. K. Kim, S. H. Hong, and Y.-J. Bang Transforming Growth Factor-{beta}1 Induces Apoptosis through Fas Ligand-independent Activation of the Fas Death Pathway in Human Gastric SNU-620 Carcinoma Cells Mol. Biol. Cell, February 1, 2004; 15(2): 420 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wu, Y. Yang, C. Wang, M. A. Davoli, M. D'Amico, A. Li, K. Cveklova, Z. Kozmik, M. P. Lisanti, R. G. Russell, et al. DACH1 Inhibits Transforming Growth Factor-{beta} Signaling through Binding Smad4 J. Biol. Chem., December 19, 2003; 278(51): 51673 - 51684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Muraoka, Y. Koh, L. R. Roebuck, M. E. Sanders, D. Brantley-Sieders, A. E. Gorska, H. L. Moses, and C. L. Arteaga Increased Malignancy of Neu-Induced Mammary Tumors Overexpressing Active Transforming Growth Factor {beta}1 Mol. Cell. Biol., December 1, 2003; 23(23): 8691 - 8703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tian, S. DaCosta Byfield, W. T. Parks, S. Yoo, A. Felici, B. Tang, E. Piek, L. M. Wakefield, and A. B. Roberts Reduction in Smad2/3 Signaling Enhances Tumorigenesis but Suppresses Metastasis of Breast Cancer Cell Lines Cancer Res., December 1, 2003; 63(23): 8284 - 8292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Woodhouse, A. Fisher, R. W. Bandle, B. Bryant-Greenwood, L. Charboneau, E. F. Petricoin III, and L. A. Liotta Drosophila screening model for metastasis: Semaphorin 5c is required for l(2)gl cancer phenotype PNAS, September 30, 2003; 100(20): 11463 - 11468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Imoto, K. Sugiyama, R. Muromoto, N. Sato, T. Yamamoto, and T. Matsuda Regulation of Transforming Growth Factor-{beta} Signaling by Protein Inhibitor of Activated STAT, PIASy through Smad3 J. Biol. Chem., September 5, 2003; 278(36): 34253 - 34258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Song, S. C. Cornelius, and D. Danielpour Development and Characterization of DP-153, a Nontumorigenic Prostatic Cell Line That Undergoes Malignant Transformation by Expression of Dominant-negative Transforming Growth Factor {beta} Receptor Type II Cancer Res., August 1, 2003; 63(15): 4358 - 4367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Roberts and L. M. Wakefield The two faces of transforming growth factor {beta} in carcinogenesis PNAS, July 22, 2003; 100(15): 8621 - 8623. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Plaut, A. J. Dean, T. A. Patnode, and T. M. Casey Effect of Transforming Growth Factor-beta (TGF-{beta}) on Mammary Development J Dairy Sci, July 1, 2003; 86(13_suppl): E16 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. DUFF, C. LI, J. M. GARLAND, and S. KUMAR CD105 is important for angiogenesis: evidence and potential applications FASEB J, June 1, 2003; 17(9): 984 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Bates and A. M. Mercurio Tumor Necrosis Factor-{alpha} Stimulates the Epithelial-to-Mesenchymal Transition of Human Colonic Organoids Mol. Biol. Cell, May 1, 2003; 14(5): 1790 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Suh, A. B. Roberts, S. Birkey Reffey, K. Miyazono, S. Itoh, P. t. Dijke, E. H. Heiss, A. E. Place, R. Risingsong, C. R. Williams, et al. Synthetic Triterpenoids Enhance Transforming Growth Factor {beta}/Smad Signaling Cancer Res., March 15, 2003; 63(6): 1371 - 1376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Baldwin, H. Tran, and B. Y. Karlan Loss of c-myc Repression Coincides with Ovarian Cancer Resistance to Transforming Growth Factor {beta} Growth Arrest Independent of Transforming Growth Factor {beta}/Smad Signaling Cancer Res., March 15, 2003; 63(6): 1413 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sasaki, H. Suzuki, K. Yagi, M. Furuhashi, R. Yao, S. Susa, T. Noda, Y. Arai, K. Miyazono, and M. Kato Lymphoid Enhancer Factor 1 Makes Cells Resistant to Transforming Growth Factor {beta}-induced Repression of c-myc Cancer Res., February 15, 2003; 63(4): 801 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dumont, A. V. Bakin, and C. L. Arteaga Autocrine Transforming Growth Factor-beta Signaling Mediates Smad-independent Motility in Human Cancer Cells J. Biol. Chem., January 24, 2003; 278(5): 3275 - 3285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Flanders and J. K. Burmester Medical Applications of Transforming Growth Factor-{beta} Clin. Med. Res., January 1, 2003; 1(1): 13 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Suh, W. W. Lamph, A. L. Glasebrook, T. A. Grese, A. D. Palkowitz, C. R. Williams, R. Risingsong, M. R. Farris, R. A. Heyman, and M. B. Sporn Prevention and Treatment of Experimental Breast Cancer with the Combination of a New Selective Estrogen Receptor Modulator, Arzoxifene, and a New Rexinoid, LG 100268 Clin. Cancer Res., October 1, 2002; 8(10): 3270 - 3275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Robetorye, S. D. Bohling, J. W. Morgan, G. C. Fillmore, M. S. Lim, and K. S. J. Elenitoba-Johnson Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18) J. Mol. Diagn., August 1, 2002; 4(3): 123 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Y. Qin, S. S. Lam, J. J. Correia, and K. Lin Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control Genes & Dev., August 1, 2002; 16(15): 1950 - 1963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Attisano and J. L. Wrana Signal Transduction by the TGF-beta Superfamily Science, May 31, 2002; 296(5573): 1646 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Fernandez, S. Amoroso, S. Sharpe, G. M. Jones, V. Bliskovski, A. Kovalchuk, L. M. Wakefield, S.-J. Kim, M. Potter, and J. J. Letterio Disruption of Transforming Growth Factor {beta} Signaling by a Novel Ligand-dependent Mechanism J. Exp. Med., May 20, 2002; 195(10): 1247 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dennler, M.-J. Goumans, and P. ten Dijke Transforming growth factor {beta} signal transduction J. Leukoc. Biol., May 1, 2002; 71(5): 731 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Moustakas, S. Souchelnytskyi, and C.-H. Heldin Smad regulation in TGF-{beta} signal transduction J. Cell Sci., March 14, 2002; 114(24): 4359 - 4369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-C. Kim, M. Mamura, K. S. Choi, B. Calabretta, and S.-J. Kim Transforming Growth Factor {beta}1 Induces Apoptosis through Cleavage of BAD in a Smad3-Dependent Mechanism in FaO Hepatoma Cells Mol. Cell. Biol., March 1, 2002; 22(5): 1369 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-a. Yang, B. Tang, G. Robinson, L. Hennighausen, S. G. Brodie, C.-X. Deng, and L. M. Wakefield Smad3 in the Mammary Epithelium Has a Nonredundant Role in the Induction of Apoptosis, but not in the Regulation of Proliferation or Differentiation by Transforming Growth Factor-{beta} Cell Growth Differ., March 1, 2002; 13(3): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Flanders, C. D. Sullivan, M. Fujii, A. Sowers, M. A. Anzano, A. Arabshahi, C. Major, C. Deng, A. Russo, J. B. Mitchell, et al. Mice Lacking Smad3 Are Protected Against Cutaneous Injury Induced by Ionizing Radiation Am. J. Pathol., March 1, 2002; 160(3): 1057 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Fan, G. Valdimarsdottir, J. Larsson, A. Brun, M. Magnusson, S. E. Jacobsen, P. ten Dijke, and S. Karlsson Transient Disruption of Autocrine TGF-{beta} Signaling Leads to Enhanced Survival and Proliferation Potential in Single Primitive Human Hemopoietic Progenitor Cells J. Immunol., January 15, 2002; 168(2): 755 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Bakin, C. Rinehart, A. K. Tomlinson, and C. L. Arteaga p38 mitogen-activated protein kinase is required for TGF{beta}-mediated fibroblastic transdifferentiation and cell migration J. Cell Sci., January 8, 2002; 115(15): 3193 - 3206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Docagne, N. Colloc'h, V. Bougueret, M. Page, J. Paput, M. Tripier, P. Dutartre, E. T. MacKenzie, A. Buisson, S. Komesli, et al. A Soluble Transforming Growth Factor-beta (TGF-beta ) Type I Receptor Mimics TGF-beta Responses J. Biol. Chem., November 30, 2001; 276(49): 46243 - 46250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuda, T. Yamamoto, A. Muraguchi, and F. Saatcioglu |