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.
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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
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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.
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The authors declare that they have no conflicts of interest.
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Saitoh, M. (2018). Regulation of EMT by TGF-β Signaling in Cancer Cells. In: Shinomiya, N., Kataoka, H., Xie, Q. (eds) Regulation of Signal Transduction in Human Cell Research. Current Human Cell Research and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-10-7296-3_4
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