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Regulation of EMT by TGF-β Signaling in Cancer Cells

Chapter
Part of the Current Human Cell Research and Applications book series (CHCRA)

Abstract

The transforming growth factor (TGF)-β pathway mediates a broad spectrum of cellular processes and is involved in several diseases, including cancer. TGF-β can suppress tumorigenesis by inhibiting cell-cycle progression and stimulating apoptosis in the early stages of cancer, suggesting that it acts as a tumor suppressor during cancer initiation. However, TGF-β can also act as a tumor promoter at later stages of cancer progression. TGF-β plays fundamental roles in cancer cells and various types of cells in the cancer microenvironment, leading to angiogenesis, suppression of antitumor immunity, fibroblast differentiation, extracellular matrix deposition, and induction of the epithelial–mesenchymal transition (EMT). The EMT plays crucial roles in appropriate embryonic development and also functions in adults during wound healing, organ fibrosis, and tumor progression. Many secreted factors are implicated in this process. Among them, TGF-β induces the EMT by propagating intracellular signals and activating transcription factors. This review describes new insights into the molecular mechanisms underlying induction of the EMT by TGF-β in cooperation with signals from growth factors and oncogenic signals such as Ras and also discusses the signals that induce the EMT through transcriptional and posttranscriptional regulation.

Keywords

TGF-β Smad Ras Snail 

Abbreviations

EMT

Epithelial–mesenchymal transition

TGF-β

Transforming growth factor-β

SIP1

Smad-interacting protein 1

δEF1

δ-crystallin/E2-box factor 1

R-Smad

Receptor-regulated Smad

Notes

Acknowledgments

We would like to thank Dr. K. Sakamoto, Dr. R. Nakamura, Dr. T. Shirakihara, Dr. K. Horiguchi, Dr. K. Miyazono, and the member of Biochemistry Laboratory (University of Yamanashi) for their collaboration. This work was supported by JSPS KAKENHI Grant Number JP15H05018.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Biological ChemistryCenter for Medical Education and Sciences, Interdisciplinary Graduate School of Medicine, University of YamanashiYamanashiJapan

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