TGF? Back to the Future: Revisiting its Role as a Transforming Growth Factor

 Abstract

TGF ? 1 was initially identified in culture media from transformed cells as part of a factor that could produce a transformed phenotype in a nontransformed cell line. Subsequently this activity was separated into TGF? and TGF? an EGF receptor ligand. With the discovery that TGF ? 1 was a potent growth inhibitor of epithelial cells, and the identification of inactivating mutations within the TGF ? 1 signaling pathway in cancers it became clear that TGF ? 1 signaling is a tumor suppressor pathway for early stages of cancer. However many human carcinomas overexpress TGF ? 1 and this is associated with poor patient prognosis and increased frequency of metastasis. Similar results have been obtained with tumor cell lines and experimental animal models. Thus stage specific duality of function is the emerging paradigm for the role of TGF ? 1 in cancer. This review will focus on the evidence for TGF ? 1 as a tumor promoting and metastasis factor and examine the biological and molecular basis for these effects. It is proposed that the switch from tumor suppressor to oncogene reflects genetic or epigenetic alterations in signaling pathways in tumor cells that alter the readout from the TGF ? 1 pathway.

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Pages
276 - 283
doi
10.4161/cbt.3.3.849
Type
Review
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TGF? Back to the Future: Revisiting its Role as a Transforming Growth Factor