Cellular context-dependent "colors" of transforming growth factor-β signaling

Abstract

Transforming growth factor (TGF)-β signaling has interesting characteristics in the context of cancer. Although perturbations of TGF-β signaling are strongly implicated in cancer progression, TGF-β signaling has both tumor-suppressive and tumor-promoting effects. For example, TGF-β inhibits cancer cell proliferation in some cellular contexts, but promotes it in others. Although several approaches to treating cancer have been considered using TGF-β-based therapeutic strategies, the contradictory behaviors of TGF-β have made these approaches complex. To put them to practical use, either the tumor-suppressive or tumor-promoting arm needs to be specifically manipulated. However, there is virtually no method to specifically regulate a certain cell response induced by TGF-β. In this review, we first consider the basic machinery of TGF-β signaling, and describe several cell responses induced by TGF-β stimulation in specific contexts. Mechanisms by which TGF-β can induce several responses in a cellular context-dependent fashion are discussed with established paradigms and models. We also address perspectives on the specific control of only a subset of numerous cell responses induced by TGF-β stimulation. Such methods will aid specific regulation of either the tumor-suppressive or tumor-promoting arm of the TGF-β pathway and in realization of TGF-β-based treatment of malignant tumors. © 2010 Japanese Cancer Association.