UTX epigenetically regulates epithelial-mesenchymal transition-associated breast cancer stem cell properties independently of EZH2
DC Field | Value | Language |
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dc.contributor.author | Choi, Hee-Joo | - |
dc.contributor.author | Park, Ji-Hye | - |
dc.contributor.author | Park, Mi-Kyung | - |
dc.contributor.author | Lee, Chang-Hoon | - |
dc.contributor.author | Lee, Jeong-Yeon | - |
dc.contributor.author | Kong, Gu | - |
dc.date.accessioned | 2022-04-01T09:38:56Z | - |
dc.date.available | 2022-04-01T09:38:56Z | - |
dc.date.created | 2021-12-30 | - |
dc.date.issued | 2014-10-01 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/136264 | - |
dc.description.abstract | UTX is a histone H3 lysine 27 (H3K27) demethylase that can antagonize a histone methyltransferase EZH2. Although H3K27 trimethylation by EZH2 has been involved in cancer-related biological processes including tumorigenesis, invasion, and stemness, the role of UTX in cancer progression has not been identified yet. In this study, we demonstrated an EZH2-independent tumor suppressive function of UTX in breast cancer. We found that loss of UTX enhanced self-renewal and tumorigenicity of breast cancer stem cells (CSCs) and also promoted CSC-associated epithelial-mesenchymal transition (EMT) through upregulating EMT-transcription factors (EMT-TFs), Snail, ZEB1 and ZEB2. Moreover, UTX positively regulated E-cadherin, a key marker of EMT, via these EMT-TFs. Notably, we identified that UTX facilitated epigenetic silencing of EMT-TFs by cooperating with c-Myc and various epigenetic modulators independently of EZH2. In the promoter regions of EMT-TFs, the levels of histone H3K4 methylation and H3 acetylation were inhibited by UTX. We also found that UTX formed a transcriptional repressive complex with LSD1, HDAC1, and DNMT1 for recruiting them to the promoters of EMT-TFs, while loss of UTX led to recruitment of c-Myc and p300 transcriptional active complex to these promoters. These effects were dependent on c-Myc, as UTX knockdown-induced epigenetic alterations of EMT-TFs and breast cancer stemness were reversed by siRNA-mediated c-Myc repression. Taken together, these data indicated that UTX negatively regulates EMT-induced breast CSCs by epigenetically repressing EMT-TFs independently of H3K27 methylation, suggesting a novel tumor suppressive role of UTX in breast cancer. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.title | UTX epigenetically regulates epithelial-mesenchymal transition-associated breast cancer stem cell properties independently of EZH2 | - |
dc.type | Conference | - |
dc.contributor.affiliatedAuthor | Kong, Gu | - |
dc.identifier.wosid | 000349910205390 | - |
dc.identifier.bibliographicCitation | 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR) | - |
dc.relation.isPartOf | 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR) | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
dc.citation.title | 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR) | - |
dc.citation.conferencePlace | US | - |
dc.citation.conferencePlace | San Diego, CA | - |
dc.citation.conferenceDate | 2014-04-05 | - |
dc.type.rims | CONF | - |
dc.description.journalClass | 1 | - |
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