Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis
DC Field | Value | Language |
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dc.contributor.author | Sujin Park | - |
dc.contributor.author | Mossmann, Dirk | - |
dc.contributor.author | Chen, Qian | - |
dc.contributor.author | Wang, Xueya | - |
dc.contributor.author | Dazert, Eva | - |
dc.contributor.author | Colombi, Marco | - |
dc.contributor.author | Schmidt, Alexander | - |
dc.contributor.author | Ryback, Brendan | - |
dc.contributor.author | Ng, Charlotte K. Y. | - |
dc.contributor.author | Terracciano, Luigi M. | - |
dc.contributor.author | Heim, Markus H. | - |
dc.contributor.author | Hall, Michael N. | - |
dc.date.accessioned | 2023-01-26T02:29:10Z | - |
dc.date.available | 2023-01-26T02:29:10Z | - |
dc.date.created | 2023-01-25 | - |
dc.date.issued | 2022-11 | - |
dc.identifier.issn | 1097-2765 | - |
dc.identifier.uri | https://pr.ibs.re.kr/handle/8788114/12534 | - |
dc.description.abstract | 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 carci-noma (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 synthe-sis 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 find-ings causally link transcriptional reprogramming of acetyl-CoA metabolism, dedifferentiation, and cancer. | - |
dc.language | 영어 | - |
dc.publisher | CELL PRESS | - |
dc.title | Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.identifier.wosid | 000902024900009 | - |
dc.identifier.scopusid | 2-s2.0-85141766011 | - |
dc.identifier.rimsid | 79760 | - |
dc.contributor.affiliatedAuthor | Sujin Park | - |
dc.identifier.doi | 10.1016/j.molcel.2022.10.027 | - |
dc.identifier.bibliographicCitation | MOLECULAR CELL, v.82, no.22, pp.4246 - 4261 | - |
dc.relation.isPartOf | MOLECULAR CELL | - |
dc.citation.title | MOLECULAR CELL | - |
dc.citation.volume | 82 | - |
dc.citation.number | 22 | - |
dc.citation.startPage | 4246 | - |
dc.citation.endPage | 4261 | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | POOR-PROGNOSIS | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | CD44 | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.subject.keywordPlus | SYNTHETASE | - |
dc.subject.keywordPlus | SIRT3 | - |