Abstract
The resistance to growth inhibition commonly observed in a variety of TGFb disabled human cancers, the potential role of TGFb in the exacerbation of malignancy and the effects of TGFb in suppressing the immune system, all emphasize the importance of pathways mediated by this polypeptide to the neoplastic process. Early investigations to understand the molecular basis of cancer due to defects in TGFb signaling were concentrated on examining the abundance of biologically active TGFb and its binding to TGFb receptors. However, major breakthroughs in understanding the molecular basis of the TGFb mediated effects in cancer came from genetic evidence for inactivation of the various players in its signaling cascade. The vast majority of current evidence is derived from the identification of mutations causing structural defects in TGFb receptors and Smad genes, the downstream effectors of the TGFb signaling pathway that have emerged from the analysis of human cancers. The involvement of Smads at the receptor level upon activation by a TGFb bound receptor, their participation in signal transmission to the nucleus and their direct roles in the regulation of target genes have made the various Smad genes critical targets for inactivation of TGFb signaling in cancer. To date, eight human homologues of the Smad genes have been identified and are classified into three distinct classes based on their structure and function. In this review, we discuss TGFb signaling via the Smads and the known and predicted points at which TGFb signaling could become altered in human cancer.
Current Genomics
Title: TGFb and its Smad Connection to Cancer
Volume: 3 Issue: 5
Author(s): S. Thiagalingam, K- h. Cheng, R. L. Foy, H. J. Lee, D. Chinnappan and J. F. Ponte
Affiliation:
Abstract: The resistance to growth inhibition commonly observed in a variety of TGFb disabled human cancers, the potential role of TGFb in the exacerbation of malignancy and the effects of TGFb in suppressing the immune system, all emphasize the importance of pathways mediated by this polypeptide to the neoplastic process. Early investigations to understand the molecular basis of cancer due to defects in TGFb signaling were concentrated on examining the abundance of biologically active TGFb and its binding to TGFb receptors. However, major breakthroughs in understanding the molecular basis of the TGFb mediated effects in cancer came from genetic evidence for inactivation of the various players in its signaling cascade. The vast majority of current evidence is derived from the identification of mutations causing structural defects in TGFb receptors and Smad genes, the downstream effectors of the TGFb signaling pathway that have emerged from the analysis of human cancers. The involvement of Smads at the receptor level upon activation by a TGFb bound receptor, their participation in signal transmission to the nucleus and their direct roles in the regulation of target genes have made the various Smad genes critical targets for inactivation of TGFb signaling in cancer. To date, eight human homologues of the Smad genes have been identified and are classified into three distinct classes based on their structure and function. In this review, we discuss TGFb signaling via the Smads and the known and predicted points at which TGFb signaling could become altered in human cancer.
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Cite this article as:
Thiagalingam S., Cheng h. K-, Foy L. R., Lee J. H., Chinnappan D. and Ponte F. J., TGFb and its Smad Connection to Cancer, Current Genomics 2002; 3 (5) . https://dx.doi.org/10.2174/1389202023350291
DOI https://dx.doi.org/10.2174/1389202023350291 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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