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Role of the epithelial-mesenchymal transition and its effects on embryonic stem cells.

Kim YS, Yi BR, Kim NH, Choi KC - Exp. Mol. Med. (2014)

Bottom Line: These transcription factors repress the expression of epithelial markers, for example, E-cadherin, rearrange the cytoskeleton and promote the expression of mesenchymal markers, such as vimentin, fibronectin and other EMT-activating transcription factors.Signaling pathways that induce EMT, including transforming growth factor-β, Wnt/glycogen synthase kinase-3β, Notch and receptor tyrosine kinase signaling pathways, interact with each other for the regulation of this process.In this review, we describe the underlying mechanisms of important EMT factors, indicating a precise role for EMT in ESCs, and characterize the relationship between EMT and ESCs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.

ABSTRACT
The epithelial-mesenchymal transition (EMT) is important for embryonic development and the formation of various tissues or organs. However, EMT dysfunction in normal cells leads to diseases, such as cancer or fibrosis. During the EMT, epithelial cells are converted into more invasive and active mesenchymal cells. E-box-binding proteins, including Snail, ZEB and helix-loop-helix family members, serve as EMT-activating transcription factors. These transcription factors repress the expression of epithelial markers, for example, E-cadherin, rearrange the cytoskeleton and promote the expression of mesenchymal markers, such as vimentin, fibronectin and other EMT-activating transcription factors. Signaling pathways that induce EMT, including transforming growth factor-β, Wnt/glycogen synthase kinase-3β, Notch and receptor tyrosine kinase signaling pathways, interact with each other for the regulation of this process. Although the mechanism(s) underlying EMT in cancer or embryonic development have been identified, the mechanism(s) in embryonic stem cells (ESCs) remain unclear. In this review, we describe the underlying mechanisms of important EMT factors, indicating a precise role for EMT in ESCs, and characterize the relationship between EMT and ESCs.

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Signaling pathways that induce epithelial–mesenchymal transition (EMT). Transforming growth factor (TGF)-β might affect both Smad-dependent and -independent pathways. Smad2 and Wnt activate the Notch signaling pathway. The Notch receptor is cleaved, and subsequently the Notch intracellular domain (NIC) translocates into the nucleus. The role of this protein shifts from that of a repressor to an activator through binding to DNA-binding proteins, such as CBF1, Su (H) and LAG-1. Wnt signaling is initiated through the inhibition of glycogen synthase kinase (GSK)-3β. β-Catenin subsequently enters the nucleus and forms a complex with lymphoid enhancer factor/T-cell factor to control the expression of target genes. Receptor tyrosine kinase (RTK) has a critical role in the induction of these intermediates. PI3K, phosphoinositide 3-kinase.
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fig1: Signaling pathways that induce epithelial–mesenchymal transition (EMT). Transforming growth factor (TGF)-β might affect both Smad-dependent and -independent pathways. Smad2 and Wnt activate the Notch signaling pathway. The Notch receptor is cleaved, and subsequently the Notch intracellular domain (NIC) translocates into the nucleus. The role of this protein shifts from that of a repressor to an activator through binding to DNA-binding proteins, such as CBF1, Su (H) and LAG-1. Wnt signaling is initiated through the inhibition of glycogen synthase kinase (GSK)-3β. β-Catenin subsequently enters the nucleus and forms a complex with lymphoid enhancer factor/T-cell factor to control the expression of target genes. Receptor tyrosine kinase (RTK) has a critical role in the induction of these intermediates. PI3K, phosphoinositide 3-kinase.

Mentions: EMT is important for embryonic development, and this process affects metastasis and the invasion of various cancers. Several molecules, including TGF-β and other growth factors, induce EMT. These factors bind to their respective receptors and might also interact with each other. As shown in Figure 1, various signaling pathways (for example, the TGF-β, Wnt/glycogen synthase kinase-3β, Notch and RTK signaling pathways) might be critical for the induction of EMT. ESCs are pluripotent, suggesting that these cells can differentiate into many cell types (Figure 2). Although the exact mechanism(s) underlying EMT activity has not been clarified in these cells, ESCs might be controlled through EMT under various circumstances during differentiation. Transcriptional activators of EMT, such as snail and ZEB, have also been implicated in the differentiation of ESCs, and regulating factors, such as the microRNA family, specifically promoted or inhibited EMT at the pluripotent cell stage. Thus, ESCs remain at either the pluripotent stage or the more differentiated stage. EMT and regulating factors regulate the differentiation of ESCs. Because ESCs, rather than epiblast stem cells, are more undifferentiated, these cells undergo EMT differentiation, suggesting that this process contributes to naïve and primed cell types. Thus, further studies should examine the mechanism(s) underlying EMT in ESCs required to generate transgenic organisms and induced pluripotent stem cells in order to develop the treatments for diseases using stem cells.


Role of the epithelial-mesenchymal transition and its effects on embryonic stem cells.

Kim YS, Yi BR, Kim NH, Choi KC - Exp. Mol. Med. (2014)

Signaling pathways that induce epithelial–mesenchymal transition (EMT). Transforming growth factor (TGF)-β might affect both Smad-dependent and -independent pathways. Smad2 and Wnt activate the Notch signaling pathway. The Notch receptor is cleaved, and subsequently the Notch intracellular domain (NIC) translocates into the nucleus. The role of this protein shifts from that of a repressor to an activator through binding to DNA-binding proteins, such as CBF1, Su (H) and LAG-1. Wnt signaling is initiated through the inhibition of glycogen synthase kinase (GSK)-3β. β-Catenin subsequently enters the nucleus and forms a complex with lymphoid enhancer factor/T-cell factor to control the expression of target genes. Receptor tyrosine kinase (RTK) has a critical role in the induction of these intermediates. PI3K, phosphoinositide 3-kinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150931&req=5

fig1: Signaling pathways that induce epithelial–mesenchymal transition (EMT). Transforming growth factor (TGF)-β might affect both Smad-dependent and -independent pathways. Smad2 and Wnt activate the Notch signaling pathway. The Notch receptor is cleaved, and subsequently the Notch intracellular domain (NIC) translocates into the nucleus. The role of this protein shifts from that of a repressor to an activator through binding to DNA-binding proteins, such as CBF1, Su (H) and LAG-1. Wnt signaling is initiated through the inhibition of glycogen synthase kinase (GSK)-3β. β-Catenin subsequently enters the nucleus and forms a complex with lymphoid enhancer factor/T-cell factor to control the expression of target genes. Receptor tyrosine kinase (RTK) has a critical role in the induction of these intermediates. PI3K, phosphoinositide 3-kinase.
Mentions: EMT is important for embryonic development, and this process affects metastasis and the invasion of various cancers. Several molecules, including TGF-β and other growth factors, induce EMT. These factors bind to their respective receptors and might also interact with each other. As shown in Figure 1, various signaling pathways (for example, the TGF-β, Wnt/glycogen synthase kinase-3β, Notch and RTK signaling pathways) might be critical for the induction of EMT. ESCs are pluripotent, suggesting that these cells can differentiate into many cell types (Figure 2). Although the exact mechanism(s) underlying EMT activity has not been clarified in these cells, ESCs might be controlled through EMT under various circumstances during differentiation. Transcriptional activators of EMT, such as snail and ZEB, have also been implicated in the differentiation of ESCs, and regulating factors, such as the microRNA family, specifically promoted or inhibited EMT at the pluripotent cell stage. Thus, ESCs remain at either the pluripotent stage or the more differentiated stage. EMT and regulating factors regulate the differentiation of ESCs. Because ESCs, rather than epiblast stem cells, are more undifferentiated, these cells undergo EMT differentiation, suggesting that this process contributes to naïve and primed cell types. Thus, further studies should examine the mechanism(s) underlying EMT in ESCs required to generate transgenic organisms and induced pluripotent stem cells in order to develop the treatments for diseases using stem cells.

Bottom Line: These transcription factors repress the expression of epithelial markers, for example, E-cadherin, rearrange the cytoskeleton and promote the expression of mesenchymal markers, such as vimentin, fibronectin and other EMT-activating transcription factors.Signaling pathways that induce EMT, including transforming growth factor-β, Wnt/glycogen synthase kinase-3β, Notch and receptor tyrosine kinase signaling pathways, interact with each other for the regulation of this process.In this review, we describe the underlying mechanisms of important EMT factors, indicating a precise role for EMT in ESCs, and characterize the relationship between EMT and ESCs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.

ABSTRACT
The epithelial-mesenchymal transition (EMT) is important for embryonic development and the formation of various tissues or organs. However, EMT dysfunction in normal cells leads to diseases, such as cancer or fibrosis. During the EMT, epithelial cells are converted into more invasive and active mesenchymal cells. E-box-binding proteins, including Snail, ZEB and helix-loop-helix family members, serve as EMT-activating transcription factors. These transcription factors repress the expression of epithelial markers, for example, E-cadherin, rearrange the cytoskeleton and promote the expression of mesenchymal markers, such as vimentin, fibronectin and other EMT-activating transcription factors. Signaling pathways that induce EMT, including transforming growth factor-β, Wnt/glycogen synthase kinase-3β, Notch and receptor tyrosine kinase signaling pathways, interact with each other for the regulation of this process. Although the mechanism(s) underlying EMT in cancer or embryonic development have been identified, the mechanism(s) in embryonic stem cells (ESCs) remain unclear. In this review, we describe the underlying mechanisms of important EMT factors, indicating a precise role for EMT in ESCs, and characterize the relationship between EMT and ESCs.

Show MeSH
Related in: MedlinePlus