Regulation of epithelial‐to‐mesenchymal transition in hypoxia by the HIF‐1α network
Epithelial‐to‐mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF‐β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF‐1α network to explore the potential link between E...
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| Published in | FEBS letters Vol. 596; no. 3; pp. 338 - 349 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
England
01.02.2022
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| Abstract | Epithelial‐to‐mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF‐β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF‐1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF‐1α and its three targets SNAIL, TWIST, and miR‐210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT.
This study reveals the mechanism of hypoxia‐induced epithelial‐to‐mesenchymal transition (EMT) by modeling. Under aggravating hypoxia, hypoxia‐inducible factor‐1α (HIF‐1α) induces snail, twist, and miR‐210 so that three positive feedback loops are triggered sequentially to push forward EMT. Our results suggested that the number of positive feedback loops may be associated with the number of stable states in EMT. |
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| AbstractList | Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF-1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF-1α and its three targets SNAIL, TWIST, and miR-210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT.Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF-1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF-1α and its three targets SNAIL, TWIST, and miR-210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT. Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF-1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF-1α and its three targets SNAIL, TWIST, and miR-210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT. Epithelial‐to‐mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF‐β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF‐1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF‐1α and its three targets SNAIL, TWIST, and miR‐210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT. This study reveals the mechanism of hypoxia‐induced epithelial‐to‐mesenchymal transition (EMT) by modeling. Under aggravating hypoxia, hypoxia‐inducible factor‐1α (HIF‐1α) induces snail, twist, and miR‐210 so that three positive feedback loops are triggered sequentially to push forward EMT. Our results suggested that the number of positive feedback loops may be associated with the number of stable states in EMT. |
| Author | Wang, Wei Zhang, Xiao‐Peng Wang, Hang‐Yu |
| Author_xml | – sequence: 1 givenname: Hang‐Yu surname: Wang fullname: Wang, Hang‐Yu organization: Nanjing University – sequence: 2 givenname: Xiao‐Peng orcidid: 0000-0001-8170-1236 surname: Zhang fullname: Zhang, Xiao‐Peng email: zhangxp@nju.edu.cn organization: Nanjing University – sequence: 3 givenname: Wei surname: Wang fullname: Wang, Wei email: zhangxp@nju.edu.cn, wangwei@nju.edu.cn organization: Nanjing University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34905218$$D View this record in MEDLINE/PubMed |
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| Snippet | Epithelial‐to‐mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF‐β network.... Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-β network.... |
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| SubjectTerms | Cell Hypoxia Epithelial-Mesenchymal Transition - genetics epithelial‐to‐mesenchymal transition Feedback, Physiological HIF‐1α network Humans hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism intermediate state metastasis MicroRNAs - genetics MicroRNAs - metabolism Models, Biological Nuclear Proteins positive feedback loop Snail Family Transcription Factors - genetics Snail Family Transcription Factors - metabolism topology Twist-Related Protein 1 - genetics Twist-Related Protein 1 - metabolism |
| Title | Regulation of epithelial‐to‐mesenchymal transition in hypoxia by the HIF‐1α network |
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