Open AccessCellular context‐dependent “colors” of transforming growth factor‐β signaling
Author(s) -
Ikushima Hiroaki,
Miyazono Kohei
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01441.x
Subject(s) - transforming growth factor , context (archaeology) , signal transduction , cell growth , cancer research , cancer , biology , tumor progression , cell signaling , transforming growth factor beta , stimulation , cell , microbiology and biotechnology , neuroscience , genetics , paleontology
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. ( Cancer Sci 2010; 101: 306–312)