Cellular context-dependent "colors" of transforming growth factor-beta signaling.
Transforming growth factor (TGF)-beta signaling has interesting characteristics in the context of cancer. Although perturbations of TGF-beta signaling are strongly implicated in cancer progression, TGF-beta signaling has both tumor-suppressive and tumor-promoting effects. For example, TGF-beta inhibits cancer cell proliferation in some cellular contexts, but promotes it in others. Although several approaches to treating cancer have been considered using TGF-beta-based therapeutic strategies, the contradictory behaviors of TGF-beta 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-beta. In this review, we first consider the basic machinery of TGF-beta signaling, and describe several cell responses induced by TGF-beta stimulation in specific contexts. Mechanisms by which TGF-beta 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-beta stimulation. Such methods will aid specific regulation of either the tumor-suppressive or tumor-promoting arm of the TGF-beta pathway and in realization of TGF-beta-based treatment of malignant tumors.
Ikushima
Hiroaki
H
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Miyazono
Kohei
K
D000818:Animals; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D009369:Neoplasms / Q000517:prevention & control / Q000628:therapy; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D035683:MicroRNAs; D016212:Transforming Growth Factor beta