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The short-chain fatty acid acetate modulates epithelial-to-mesenchymal transition
Normal tissue and organ morphogenesis requires epithelial cell plasticity and conversion to a mesenchymal phenotype through a tightly regulated process-epithelial-to-mesenchymal transition (EMT). Alterations of EMT go far beyond cell-lineage segregation and contribute to pathologic conditions such a...
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Published in: | Molecular biology of the cell 2022-07, Vol.33 (8), p.br13 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Normal tissue and organ morphogenesis requires epithelial cell plasticity and conversion to a mesenchymal phenotype through a tightly regulated process-epithelial-to-mesenchymal transition (EMT). Alterations of EMT go far beyond cell-lineage segregation and contribute to pathologic conditions such as cancer. EMT is subject to intersecting control pathways; however, EMT's metabolic mechanism remains poorly understood. Here, we demonstrate that transforming growth factor β (TGF-β)-induced EMT is accompanied by decreased fatty acid oxidation (FAO) and reduced acetyl-coenzyme A (acetyl-CoA) levels. Acetyl-CoA is a central metabolite and the sole donor of acetyl groups to acetylate key proteins. Further, the short-chain fatty acid acetate increases acetyl-CoA levels--robustly inhibiting EMT and cancer cell migration. Acetate can restore EMT-associated α-tubulin acetylation levels, increasing microtubule stability. Transcriptome profiling and flow cytometric analysis show that acetate inhibits the global gene expression program associated with EMT and the EMT-associated G1 cell cycle arrest. Taken together, these results demonstrate that acetate is a potent metabolic regulator of EMT and that therapeutic manipulation of acetate metabolism could provide the basis for treating a wide range of EMT-linked pathological conditions, including cancer. |
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ISSN: | 1059-1524 1939-4586 |
DOI: | 10.1091/mbc.E22-02-0066 |