| First Author | Park S | Year | 2022 |
| Journal | Mol Cell | Volume | 82 |
| Issue | 22 | Pages | 4246-4261.e11 |
| PubMed ID | 36400009 | Mgi Jnum | J:351711 |
| Mgi Id | MGI:7398074 | Doi | 10.1016/j.molcel.2022.10.027 |
| Citation | Park S, et al. (2022) Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis. Mol Cell 82(22):4246-4261.e11 |
| abstractText | Acetyl-coenzyme A (acetyl-CoA) plays an important role in metabolism, gene expression, signaling, and other cellular processes via transfer of its acetyl group to proteins and metabolites. However, the synthesis and usage of acetyl-CoA in disease states such as cancer are poorly characterized. Here, we investigated global acetyl-CoA synthesis and protein acetylation in a mouse model and patient samples of hepatocellular carcinoma (HCC). Unexpectedly, we found that acetyl-CoA levels are decreased in HCC due to transcriptional downregulation of all six acetyl-CoA biosynthesis pathways. This led to hypo-acetylation specifically of non-histone proteins, including many enzymes in metabolic pathways. Importantly, repression of acetyl-CoA synthesis promoted oncogenic dedifferentiation and proliferation. Mechanistically, acetyl-CoA synthesis was repressed by the transcription factors TEAD2 and E2A, previously unknown to control acetyl-CoA synthesis. Knockdown of TEAD2 and E2A restored acetyl-CoA levels and inhibited tumor growth. Our findings causally link transcriptional reprogramming of acetyl-CoA metabolism, dedifferentiation, and cancer. |
