Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 김이준 | * |
dc.date.accessioned | 2024-02-01T16:30:48Z | - |
dc.date.available | 2024-02-01T16:30:48Z | - |
dc.date.issued | 2024 | * |
dc.identifier.issn | 2666-3791 | * |
dc.identifier.other | OAK-34787 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/266926 | - |
dc.description.abstract | Chondrosarcomas represent the second most common primary bone malignancy. Despite the vulnerability of chondrosarcoma cells to nicotinamide adenine dinucleotide (NAD+) depletion, targeting the NAD+ synthesis pathway remains challenging due to broad implications in biological processes. Here, we establish SIRT1 as a central mediator reinforcing the dependency of chondrosarcoma cells on NAD+ metabolism via HIF-2a-mediated transcriptional reprogramming. SIRT1 knockdown abolishes aggressive phenotypes of chondrosarcomas in orthotopically transplanted tumors in mice. Chondrosarcoma cells thrive under glucose starvation by accumulating NAD+ and subsequently activating the SIRT1-HIF-2a axis. Decoupling this link via SIRT1 inhibition unleashes apoptosis and suppresses tumor progression in conjunction with chemotherapy. Unsupervised clustering analysis identifies a high -risk chondrosarcoma patient subgroup characterized by the upregulation of NAD+ biosynthesis genes. Finally, SIRT1 inhibition abolishes HIF-2a transcriptional activity and sensitizes chondrosarcoma cells to doxorubicin-induced cytotoxicity, irrespective of underlying pathways to accumulate intracellular NAD+. We provide system -level guidelines to develop therapeutic strategies for chondrosarcomas. | * |
dc.language | English | * |
dc.publisher | CELL PRESS | * |
dc.title | Decoupling NAD plus metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2a axis | * |
dc.type | Article | * |
dc.relation.issue | 1 | * |
dc.relation.volume | 5 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | CELL REPORTS MEDICINE | * |
dc.identifier.doi | 10.1016/j.xcrm.2023.101342|http://dx.doi.org/10.1016/j.xcrm.2023.101342 | * |
dc.identifier.wosid | WOS:001170850500001 | * |
dc.identifier.scopusid | 2-s2.0-85182574588 | * |
dc.author.google | Suh, Jooyeon | * |
dc.author.google | Kim, Hyeonkyeong | * |
dc.author.google | Min, Jiyun | * |
dc.author.google | Yeon, Hyun Ju | * |
dc.author.google | Hemberg, Martin | * |
dc.author.google | Scimeca, Luca | * |
dc.author.google | Wu, Ming-Ru | * |
dc.author.google | Kang, Hyun Guy | * |
dc.author.google | Kim, Yi-Jun | * |
dc.author.google | Kim, Jin-Hong | * |
dc.contributor.scopusid | 김이준(56714252700) | * |
dc.date.modifydate | 20240502144901 | * |