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TGF-β signaling in tumor suppression and cancer progression

An Erratum to this article was published on 01 November 2001

Abstract

Epithelial and hematopoietic cells have a high turnover and their progenitor cells divide continuously, making them prime targets for genetic and epigenetic changes that lead to cell transformation and tumorigenesis. The consequent changes in cell behavior and responsiveness result not only from genetic alterations such as activation of oncogenes or inactivation of tumor suppressor genes, but also from altered production of, or responsiveness to, stimulatory or inhibitory growth and differentiation factors. Among these, transforming growth factor β (TGF-β) and its signaling effectors act as key determinants of carcinoma cell behavior. The autocrine and paracrine effects of TGF-β on tumor cells and the tumor micro-environment exert both positive and negative influences on cancer development. Accordingly, the TGF-β signaling pathway has been considered as both a tumor suppressor pathway and a promoter of tumor progression and invasion. Here we evaluate the role of TGF-β in tumor development and attempt to reconcile the positive and negative effects of TGF-β in carcinogenesis.

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Figure 1: TGF-β-induced signaling through Smads, and several non-Smad signaling mechanisms.
Figure 2: TGF-β acts on both the tumor cell and its environment.
Figure 3: Alternative roles for TGF-β signaling in cancer progression.

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Acknowledgements

It is impossible to mention every important contribution to our understanding of the mechanisms of TGF-β signaling and its role in cancer, and we apologize to those investigators whose contributions could not be acknowledged. Relevant research in the laboratories of the authors is funded by NIH grants to R.D.; NIH, March of Dimes and American Heart Association grants to R.J.A.; and an NIH grant to A.B. We thank J. Qing for the design and drawing of Fig. 1, and A. Roberts, B. Lechleider and C. Arteaga for their comments.

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Derynck, R., Akhurst, R. & Balmain, A. TGF-β signaling in tumor suppression and cancer progression. Nat Genet 29, 117–129 (2001). https://doi.org/10.1038/ng1001-117

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