Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer
Summary: Cancer metastasis relies on an orchestration of traits driven by different interacting functional modules, including metabolism and epithelial-mesenchymal transition (EMT). During metastasis, cancer cells can acquire a hybrid metabolic phenotype (W/O) by increasing oxidative phosphorylation...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222019927 |
| _version_ | 1797946142374232064 |
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| author | Madeline Galbraith Herbert Levine José N. Onuchic Dongya Jia |
| author_facet | Madeline Galbraith Herbert Levine José N. Onuchic Dongya Jia |
| author_sort | Madeline Galbraith |
| collection | DOAJ |
| description | Summary: Cancer metastasis relies on an orchestration of traits driven by different interacting functional modules, including metabolism and epithelial-mesenchymal transition (EMT). During metastasis, cancer cells can acquire a hybrid metabolic phenotype (W/O) by increasing oxidative phosphorylation without compromising glycolysis and they can acquire a hybrid epithelial/mesenchymal (E/M) phenotype by engaging EMT. Both the W/O and E/M states are associated with high metastatic potentials, and many regulatory links coupling metabolism and EMT have been identified. Here, we investigate the coupled decision-making networks of metabolism and EMT. Their crosstalk can exhibit synergistic or antagonistic effects on the acquisition and stability of different coupled metabolism-EMT states. Strikingly, the aggressive E/M-W/O state can be enabled and stabilized by the crosstalk irrespective of these hybrid states’ availability in individual metabolism or EMT modules. Our work emphasizes the mutual activation between metabolism and EMT, providing an important step toward understanding the multifaceted nature of cancer metastasis. |
| first_indexed | 2024-04-10T21:06:16Z |
| format | Article |
| id | doaj.art-3d41f39474594e20b222c6ac491a3d0b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:06:16Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3d41f39474594e20b222c6ac491a3d0b2023-01-22T04:40:32ZengElsevieriScience2589-00422023-01-01261105719Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancerMadeline Galbraith0Herbert Levine1José N. Onuchic2Dongya Jia3Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA; Department of Physics and Astronomy, Rice University, Houston, TX77005, USACenter for Theoretical Biological Physics, Department of Physics, and Department of Bioengineering, Northeastern University, Boston, MA02115, USA; Corresponding authorCenter for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA; Department of Physics and Astronomy, Rice University, Houston, TX77005, USA; Department of Chemistry, Rice University, Houston, TX77005, USA; Department of Biosciences, Rice University, Houston, TX77005, USA; Corresponding authorCenter for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA; Corresponding authorSummary: Cancer metastasis relies on an orchestration of traits driven by different interacting functional modules, including metabolism and epithelial-mesenchymal transition (EMT). During metastasis, cancer cells can acquire a hybrid metabolic phenotype (W/O) by increasing oxidative phosphorylation without compromising glycolysis and they can acquire a hybrid epithelial/mesenchymal (E/M) phenotype by engaging EMT. Both the W/O and E/M states are associated with high metastatic potentials, and many regulatory links coupling metabolism and EMT have been identified. Here, we investigate the coupled decision-making networks of metabolism and EMT. Their crosstalk can exhibit synergistic or antagonistic effects on the acquisition and stability of different coupled metabolism-EMT states. Strikingly, the aggressive E/M-W/O state can be enabled and stabilized by the crosstalk irrespective of these hybrid states’ availability in individual metabolism or EMT modules. Our work emphasizes the mutual activation between metabolism and EMT, providing an important step toward understanding the multifaceted nature of cancer metastasis.http://www.sciencedirect.com/science/article/pii/S2589004222019927Cancer systems biologyMetabolic flux analysis |
| spellingShingle | Madeline Galbraith Herbert Levine José N. Onuchic Dongya Jia Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer iScience Cancer systems biology Metabolic flux analysis |
| title | Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer |
| title_full | Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer |
| title_fullStr | Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer |
| title_full_unstemmed | Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer |
| title_short | Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer |
| title_sort | decoding the coupled decision making of the epithelial mesenchymal transition and metabolic reprogramming in cancer |
| topic | Cancer systems biology Metabolic flux analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222019927 |
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