Epithelial Mesenchymal Transition in Embryonic Development, Tissue Repair and Cancer: A Comprehensive Overview
Abstract
:1. Introduction
2. Key Concepts and EMT Classification
3. EMT during Embryonic Development
3.1. EMT and Signaling Pathways in Gastrulation
3.2. EMT and Signaling Pathways during Neural Crest Formation
3.3. MET and Embryonic Development
4. EMT and Wound Healing, Tissue Regeneration and Organ Fibrosis
5. EMT and Cancer
5.1. EMT and Cancer Cell Survival
5.2. EMT and Disruption of Cell Junctions and Polarity
5.3. EMT Confers Stem Cell Properties
5.4. EMT and Circulating Tumor Cells
5.5. EMT and Drug Resistance to Cancer Therapy
6. Key Regulatory Molecular Mechanisms of EMT
6.1. Gene Expression Changes in EMT
6.2. Complexity in EMT Signaling Pathways
6.3. EMT and MicroRNAs
6.4. EMT and Autophagy
7. Concluding Remarks
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Types of EMT | Functions | Features | Consequences |
---|---|---|---|
I | Implantation, embryogenesis and organ development | Generates diverse cell types that may undergo an MET to form secondary epithelial cells during embryogenesis | No fibrosis; No invasion |
II | Wound healing, tissue regeneration and organ fibrosis | Generates fibroblasts and other related cells to reconstruct tissues following trauma and inflammatory injury | Fibrosis; No invasion |
III | Malignant transformation of cancer cells | Produces cancer cells that maintain many epithelial traits along with some mesenchymal traits or produce cancer cells that become fully mesenchymal | Invasion and metastasis |
Molecules | Description | References | |
---|---|---|---|
Direct E-cadherin repressors | Snail1 (Snail), Snail2 (Slug), Snail3 (Smuc) | Zinc finger proteins of the Snail superfamily | [139] |
Zeb1 (δEF1), Zeb2 (SIP1), Tcf8 | Zinc finger and E-box binding proteins of the Zeb family | [140] | |
E47 | A βHLH factor | [141] | |
Klf8 | A Krüppel-like factor | [142] | |
Indirect E-cadherin repressors | Twist1, Twist2 | Twist βHLH proteins | [131] |
GSC and Six1 | Homeobox proteins | [143,144] | |
E2.2 | A βHLH factor | [145] | |
Foxc2 | A forkhead-box protein | [146] |
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Kim, D.H.; Xing, T.; Yang, Z.; Dudek, R.; Lu, Q.; Chen, Y.-H. Epithelial Mesenchymal Transition in Embryonic Development, Tissue Repair and Cancer: A Comprehensive Overview. J. Clin. Med. 2018, 7, 1. https://doi.org/10.3390/jcm7010001
Kim DH, Xing T, Yang Z, Dudek R, Lu Q, Chen Y-H. Epithelial Mesenchymal Transition in Embryonic Development, Tissue Repair and Cancer: A Comprehensive Overview. Journal of Clinical Medicine. 2018; 7(1):1. https://doi.org/10.3390/jcm7010001
Chicago/Turabian StyleKim, Do Hyung, Tiaosi Xing, Zhibin Yang, Ronald Dudek, Qun Lu, and Yan-Hua Chen. 2018. "Epithelial Mesenchymal Transition in Embryonic Development, Tissue Repair and Cancer: A Comprehensive Overview" Journal of Clinical Medicine 7, no. 1: 1. https://doi.org/10.3390/jcm7010001