Abstract
Epithelial-mesenchymal transition (EMT) plays an important role in the development of tumor metastases by facilitating cell migration and invasion. One of the hallmarks of EMT is the diminished expression of E-cadherin and gain of mesenchymal traits, which are regulated by core EMT-inducing transcriptional factors (EMT-TFs), such as Snail/Slug, ZEB1/ZEB2, and Twist1. EMT-TFs are known to be extremely labile proteins, and their protein levels are tightly controlled by the ubiquitin-proteasome system (UPS). Several E3 ubiquitin ligases have been shown to play crucial roles in the regulation of EMT, and genetic aberrations and alterations in these ligases have been detected in human cancer. In this review, we focused on EMT-TFs, describing the UPS controlling their activities and functions in cancer. A deeper understanding of the role of UPS in the regulation of EMT will provide valuable information for the development of effective anti-metastatic drugs to modulate the malignant processes mediated by EMT.
Keywords: Deubiquitinase (DUB), E3 ubiquitin ligase, epithelial-mesenchymal transition (EMT), Snail, Slug, Twist, ubiquitinproteasome system (UPS), ZEB.
Current Cancer Drug Targets
Title:Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer
Volume: 16 Issue: 2
Author(s): Yasumichi Inoue, Yuka Itoh, Koichi Sato, Fumihiro Kawasaki, Chihiro Sumita, Takahito Tanaka, Daisuke Morishita and Hidetoshi Hayashi
Affiliation:
Keywords: Deubiquitinase (DUB), E3 ubiquitin ligase, epithelial-mesenchymal transition (EMT), Snail, Slug, Twist, ubiquitinproteasome system (UPS), ZEB.
Abstract: Epithelial-mesenchymal transition (EMT) plays an important role in the development of tumor metastases by facilitating cell migration and invasion. One of the hallmarks of EMT is the diminished expression of E-cadherin and gain of mesenchymal traits, which are regulated by core EMT-inducing transcriptional factors (EMT-TFs), such as Snail/Slug, ZEB1/ZEB2, and Twist1. EMT-TFs are known to be extremely labile proteins, and their protein levels are tightly controlled by the ubiquitin-proteasome system (UPS). Several E3 ubiquitin ligases have been shown to play crucial roles in the regulation of EMT, and genetic aberrations and alterations in these ligases have been detected in human cancer. In this review, we focused on EMT-TFs, describing the UPS controlling their activities and functions in cancer. A deeper understanding of the role of UPS in the regulation of EMT will provide valuable information for the development of effective anti-metastatic drugs to modulate the malignant processes mediated by EMT.
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Inoue Yasumichi, Itoh Yuka, Sato Koichi, Kawasaki Fumihiro, Sumita Chihiro, Tanaka Takahito, Morishita Daisuke and Hayashi Hidetoshi, Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer, Current Cancer Drug Targets 2016; 16 (2) . https://dx.doi.org/10.2174/1568009616666151112122126
DOI https://dx.doi.org/10.2174/1568009616666151112122126 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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