Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation
The neoplastic transformation of normal to metastatic cancer cells is a complex multistep process involving the progressive accumulation of interacting genetic and epigenetic changes that alter gene function and affect cell physiology and homeostasis. Epigenetic changes including DNA methylation, hi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/10/1143 |
| _version_ | 1797714094073053184 |
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| author | Georgios S. Markopoulos Eugenia Roupakia Kenneth B. Marcu Evangelos Kolettas |
| author_facet | Georgios S. Markopoulos Eugenia Roupakia Kenneth B. Marcu Evangelos Kolettas |
| author_sort | Georgios S. Markopoulos |
| collection | DOAJ |
| description | The neoplastic transformation of normal to metastatic cancer cells is a complex multistep process involving the progressive accumulation of interacting genetic and epigenetic changes that alter gene function and affect cell physiology and homeostasis. Epigenetic changes including DNA methylation, histone modifications and changes in noncoding RNA expression, and deregulation of epigenetic processes can alter gene expression during the multistep process of carcinogenesis. Cancer progression and metastasis through an ‘invasion–metastasis cascade’ involving an epithelial-to-mesenchymal cell transition (EMT), the generation of cancer stem cells (CSCs), invasion of adjacent tissues, and dissemination are fueled by inflammation, which is considered a hallmark of cancer. Chronic inflammation is generated by inflammatory cytokines secreted by the tumor and the tumor-associated cells within the tumor microenvironment. Inflammatory cytokine signaling initiates signaling pathways leading to the activation of master transcription factors (TFs) such as Smads, STAT3, and NF-κB. Moreover, the same inflammatory responses also activate EMT-inducing TF (EMT-TF) families such as Snail, Twist, and Zeb, and epigenetic regulators including DNA and histone modifying enzymes and micoRNAs, through complex interconnected positive and negative feedback loops to regulate EMT and CSC generation. Here, we review the molecular regulatory feedback loops and networks involved in inflammatory cytokine-induced EMT and CSC generation. |
| first_indexed | 2024-03-12T07:46:51Z |
| format | Article |
| id | doaj.art-5ea4c7a28cbc4c9586c59e31a7e064bf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:46:51Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5ea4c7a28cbc4c9586c59e31a7e064bf2023-09-02T20:53:17ZengMDPI AGCells2073-44092019-09-01810114310.3390/cells8101143cells8101143Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell GenerationGeorgios S. Markopoulos0Eugenia Roupakia1Kenneth B. Marcu2Evangelos Kolettas3Laboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, GreeceLaboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, GreeceBiomedical Research Division, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 45115 Ioannina, GreeceLaboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, GreeceThe neoplastic transformation of normal to metastatic cancer cells is a complex multistep process involving the progressive accumulation of interacting genetic and epigenetic changes that alter gene function and affect cell physiology and homeostasis. Epigenetic changes including DNA methylation, histone modifications and changes in noncoding RNA expression, and deregulation of epigenetic processes can alter gene expression during the multistep process of carcinogenesis. Cancer progression and metastasis through an ‘invasion–metastasis cascade’ involving an epithelial-to-mesenchymal cell transition (EMT), the generation of cancer stem cells (CSCs), invasion of adjacent tissues, and dissemination are fueled by inflammation, which is considered a hallmark of cancer. Chronic inflammation is generated by inflammatory cytokines secreted by the tumor and the tumor-associated cells within the tumor microenvironment. Inflammatory cytokine signaling initiates signaling pathways leading to the activation of master transcription factors (TFs) such as Smads, STAT3, and NF-κB. Moreover, the same inflammatory responses also activate EMT-inducing TF (EMT-TF) families such as Snail, Twist, and Zeb, and epigenetic regulators including DNA and histone modifying enzymes and micoRNAs, through complex interconnected positive and negative feedback loops to regulate EMT and CSC generation. Here, we review the molecular regulatory feedback loops and networks involved in inflammatory cytokine-induced EMT and CSC generation.https://www.mdpi.com/2073-4409/8/10/1143inflammatory cytokinesepithelial-to-mesenchymal cell transition (emt)inflammatory cytokine-induced emt (ici-emt)cancer stem cells (cscs)tumor microenvironment (tme)transcription factors (tfs)epigenetic regulatorsfeedback regulatory loops |
| spellingShingle | Georgios S. Markopoulos Eugenia Roupakia Kenneth B. Marcu Evangelos Kolettas Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation Cells inflammatory cytokines epithelial-to-mesenchymal cell transition (emt) inflammatory cytokine-induced emt (ici-emt) cancer stem cells (cscs) tumor microenvironment (tme) transcription factors (tfs) epigenetic regulators feedback regulatory loops |
| title | Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation |
| title_full | Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation |
| title_fullStr | Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation |
| title_full_unstemmed | Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation |
| title_short | Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation |
| title_sort | epigenetic regulation of inflammatory cytokine induced epithelial to mesenchymal cell transition and cancer stem cell generation |
| topic | inflammatory cytokines epithelial-to-mesenchymal cell transition (emt) inflammatory cytokine-induced emt (ici-emt) cancer stem cells (cscs) tumor microenvironment (tme) transcription factors (tfs) epigenetic regulators feedback regulatory loops |
| url | https://www.mdpi.com/2073-4409/8/10/1143 |
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