Stabilization of HDAC1 via TCL1-pAKT-CHFR axis is a key element for NANOG-mediated multi-resistance and stem-like phenotype in immune-edited tumor cells
DC Field | Value | Language |
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dc.contributor.author | Woo, Seon Rang | - |
dc.contributor.author | Lee, Hyo-Jung | - |
dc.contributor.author | Oh, Se Jin | - |
dc.contributor.author | Kim, Suyeon | - |
dc.contributor.author | Park, Sang-Hyo | - |
dc.contributor.author | Lee, Jaeyoon | - |
dc.contributor.author | Song, Kwon-Ho | - |
dc.contributor.author | Kim, Tae Woo | - |
dc.date.available | 2020-11-02T06:56:06Z | - |
dc.date.issued | 2018-09-10 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.issn | 1090-2104 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/3136 | - |
dc.description.abstract | Cancer immunoediting enriches NANOG expression in tumor cells, resulting in multi-drug resistance and stem-like phenotypes. We previously demonstrated that these NANOG-associated phenotypes are promoted through HDAC1 transcriptional upregulation. In this study, we identified that NANOG also contributes to the stabilization of HDAC1 protein through the AKT signaling pathway. NANOG-AKT axis leads to phosphor-dependent inactivation of CHFR, an E3 ligase for HDAC1 protein, and thereby inhibiting the ubiquitin-mediated degradation of HDAC1. Furthermore, AKT inhibition disrupts HDAC1 WT-mediated phenotypes but had no effect on the phenotypes mediated by HDAC1 FM, a mutant that is unable to interact with CHFR. Critically, we applied a catalytic dead mutant, HDAC1-H141A, to uncover that HDAC1 confers immune-resistance, drug-resistance and stem-like phenotype in tumor cells through its catalytic activity. Collectively, our results establish a firm molecular link in immune-edited tumor cells among NANOG, AKT, CHFR, and HDAC1, identifying HDAC1 as a molecular target in controlling NANOGHIGH immune-refractory cancer. (C) 2018 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 7 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.title | Stabilization of HDAC1 via TCL1-pAKT-CHFR axis is a key element for NANOG-mediated multi-resistance and stem-like phenotype in immune-edited tumor cells | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1016/j.bbrc.2018.07.118 | - |
dc.identifier.scopusid | 2-s2.0-85054193642 | - |
dc.identifier.wosid | 000444222100094 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.503, no.3, pp 1812 - 1818 | - |
dc.citation.title | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.volume | 503 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1812 | - |
dc.citation.endPage | 1818 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.subject.keywordPlus | CHECKPOINT PROTEIN CHFR | - |
dc.subject.keywordPlus | CANCER-IMMUNOTHERAPY | - |
dc.subject.keywordPlus | AKT | - |
dc.subject.keywordPlus | EVASION | - |
dc.subject.keywordPlus | MITOSIS | - |
dc.subject.keywordPlus | ENTRY | - |
dc.subject.keywordAuthor | NANOG | - |
dc.subject.keywordAuthor | HDAC1 | - |
dc.subject.keywordAuthor | CHFR | - |
dc.subject.keywordAuthor | Immunotherapy | - |
dc.subject.keywordAuthor | Chemoresistance | - |
dc.subject.keywordAuthor | Immuneresistance | - |
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