Abstract |
Signaling from transforming growth factor-beta ( TGF-beta) 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-beta by mutational inactivation or dysregulated expression of components in its signaling pathway. Decreased receptor function and altered ratios of the TGF-beta type I and type II receptors found in many tumor cells compromise the tumor suppressor activities of TGF-beta 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-beta 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-beta 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-beta in carcinogenesis.
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Authors | M P de Caestecker, E Piek, A B Roberts |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 92
Issue 17
Pg. 1388-402
(Sep 06 2000)
ISSN: 0027-8874 [Print] United States |
PMID | 10974075
(Publication Type: Journal Article)
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Chemical References |
- DNA-Binding Proteins
- Receptors, Transforming Growth Factor beta
- SMAD2 protein, human
- SMAD3 protein, human
- SMAD4 protein, human
- Smad2 Protein
- Smad3 Protein
- Smad4 Protein
- Trans-Activators
- Transforming Growth Factor beta
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Topics |
- Animals
- DNA-Binding Proteins
(metabolism)
- Gene Expression Regulation, Neoplastic
- Genes, Tumor Suppressor
(genetics)
- Humans
- Mutation
- Neoplasms
(genetics, metabolism)
- Receptors, Transforming Growth Factor beta
(metabolism)
- Signal Transduction
- Smad2 Protein
- Smad3 Protein
- Smad4 Protein
- Trans-Activators
(metabolism)
- Transforming Growth Factor beta
(genetics, metabolism)
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