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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/12482
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| Title: | PCAF-mediated acetylation of ISX recruits BRD4 to promote epithelial-mesenchymal transition |
| Authors: | Wang, LT;Liu, KY;Jeng, WY;Chiang, CM;Chai, CY;Chiou, SS;Huang, MS;Yokoyama, KK;Wang, SN;Huang, SK;Hsu, SH |
| Contributors: | National Institute of Environmental Health Sciences |
| Abstract: | Epigenetic regulation is important for cancer progression; however, the underlying mechanisms, particularly those involving protein acetylation, remain to be fully understood. Here, we show that p300/CBP-associated factor (PCAF)-dependent acetylation of the transcription factor intestine-specific homeobox (ISX) regulates epithelial-mesenchymal transition (EMT) and promotes cancer metastasis. Mechanistically, PCAF acetylation of ISX at lysine 69 promotes the interaction with acetylated bromodomain-containing protein 4 (BRD4) at lysine 332 in tumor cells, and the translocation of the resulting complex into the nucleus. There, it binds to promoters of EMT genes, where acetylation of histone 3 at lysines 9, 14, and 18 initiates chromatin remodeling and subsequent transcriptional activation. Ectopic ISX expression enhances EMT marker expression, including TWIST1, Snail1, and VEGF, induces cancer metastasis, but suppresses E-cadherin expression. In lung cancer, ectopic expression of PCAF-ISX-BRD4 axis components correlates with clinical metastatic features and poor prognosis. These results suggest that the PCAF-ISX-BRD4 axis mediates EMT signaling and regulates tumor initiation and metastasis. |
| Date: | 2020-01-07 |
| Relation: | EMBO Reports. 2020 Jan 7:Article number e48795. |
| Link to: | http://dx.doi.org/10.15252/embr.201948795 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1469-221X&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000505788200001 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85078073978 |
| Appears in Collections: | [黃嘯谷] 期刊論文
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| PUB31908141.pdf | | 5197Kb | Adobe PDF | 301 | View/Open |
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