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Frontiers of Medicine

, Volume 12, Issue 4, pp 387–411 | Cite as

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

  • Kohei Miyazono
  • Yoko Katsuno
  • Daizo Koinuma
  • Shogo Ehata
  • Masato Morikawa
Open Access
Review

Abstract

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.

Keywords

TGF-β EMT lung cancer pancreatic cancer latent form immune function GARP 

Notes

Acknowledgements

We thank all the members of the Molecular Pathology Laboratory at The University of Tokyo, especially Drs. Kei Takahashi, Shimpei I. Kubota, and Akihiro Katsura, for discussion. We also thank Prof. Hiroki R. Ueda (Department of Systems Pharmacology, The University of Tokyo) for collaboration. This research is supported by KAKENHI, grants-in-aid for scientific research on Innovative Area on Integrated Analysis and Regulation of Cellular Diversity (No. 17H06326, KM), from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) and Scientific Research (S) (No. 15H05774, KM) from the Japan Society for the Promotion of Science (JSPS). This work is also supported by Project for Cancer Research and Therapeutic Evolution (P-CREATE; No. 17cm0106313h0002, SE) from the Japan Agency for Medical Research and Development (AMED). KM was supported by Yasuda Medical Foundation.

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© The Author(s) 2018

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://doi.org/creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the appropriate credit is given to the original author(s) and the source, and a link is provided to the Creative Commons license, which indicates if changes are made.

Authors and Affiliations

  • Kohei Miyazono
    • 1
  • Yoko Katsuno
    • 1
  • Daizo Koinuma
    • 1
  • Shogo Ehata
    • 1
  • Masato Morikawa
    • 1
  1. 1.Department of Molecular Pathology, Graduate School of MedicineThe University of TokyoBunkyo-ku, TokyoJapan

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