Abstract
The discovery of TGF-ß has impacted our understanding of human cancer. We find many events that become deregulated are associated with TGF-ß signaling. TGF-ß has been shown to be a master regulator in every human cancer type. Accordingly, antagonists of TGF-ß signaling are emerging as therapies for cancer. Mouse models revealed the now assumed role of TGF-ß as a tumor suppressor in normal tissue, as well as TGF-ß having tumor promoting or metastatic activity once tumors progress (Muraoka et al. J Clin Invest 109:1551–1559, 2002; Pierce et al. Proc Natl Acad Sci USA 92:4254–4258, 1995; Tang et al. Nat Med 4:802–807, 1998). Mouse models have not only contributed to our understanding of TGF-ß signaling, but have also identified that the diversity of TGF-ß action is only compounded further as we consider the cells of the tumor and the tumor microenvironment. This review examines the diverse role of TGF-ß in cancer as it has been revealed through transgenic mouse models. Due to the often apparently contrary roles of TGF-ß signaling in cancer initiation, progression, and metastasis, the results from the study of mouse models may suggest better ways to target therapeutics antagonizing TGF-ß signaling.
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We apologize to those whose work we could not cite. Our work is supported by grants from the NIH GM079879 (to VRP) and CA108646 (to NAB).
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Placencio, V.R., Bhowmick, N.A. (2012). Modeling Transforming Growth Factor-ß Signaling in Cancer. In: Green, J., Ried, T. (eds) Genetically Engineered Mice for Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69805-2_19
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