1.Intracellular and extracellular TGF-β signaling in cancer: some recent topics.
Kohei MIYAZONO ; Yoko KATSUNO ; Daizo KOINUMA ; Shogo EHATA ; Masato MORIKAWA
Frontiers of Medicine 2018;12(4):387-411
Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.
Drug Discovery
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Humans
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Lung Neoplasms
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drug therapy
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immunology
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metabolism
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Membrane Proteins
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metabolism
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Pancreatic Neoplasms
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drug therapy
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immunology
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metabolism
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Signal Transduction
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drug effects
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physiology
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T-Lymphocytes, Regulatory
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metabolism
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Transforming Growth Factor beta
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antagonists & inhibitors
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immunology
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metabolism