Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis
DC Field | Value | Language |
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dc.contributor.author | Jooyeon Suh | - |
dc.contributor.author | Hyeonkyeong Kim | - |
dc.contributor.author | Jiyun Min | - |
dc.contributor.author | Hyun Ju Yeon | - |
dc.contributor.author | Hemberg, Martin | - |
dc.contributor.author | Scimeca, Luca | - |
dc.contributor.author | Wu, Ming-Ru | - |
dc.contributor.author | Kang, Hyun Guy | - |
dc.contributor.author | Kim, Yi-Jun | - |
dc.contributor.author | Jin-Hong Kim | - |
dc.date.accessioned | 2024-01-31T22:00:25Z | - |
dc.date.available | 2024-01-31T22:00:25Z | - |
dc.date.created | 2024-01-29 | - |
dc.date.issued | 2023-12 | - |
dc.identifier.uri | https://pr.ibs.re.kr/handle/8788114/14747 | - |
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-2α-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-2α 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-2α 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. © 2023 The Author(s) | - |
dc.language | 영어 | - |
dc.publisher | Cell Press | - |
dc.title | Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.identifier.wosid | 001170850500001 | - |
dc.identifier.scopusid | 2-s2.0-85182574588 | - |
dc.identifier.rimsid | 82458 | - |
dc.contributor.affiliatedAuthor | Jooyeon Suh | - |
dc.contributor.affiliatedAuthor | Hyeonkyeong Kim | - |
dc.contributor.affiliatedAuthor | Jiyun Min | - |
dc.contributor.affiliatedAuthor | Hyun Ju Yeon | - |
dc.contributor.affiliatedAuthor | Jin-Hong Kim | - |
dc.identifier.doi | 10.1016/j.xcrm.2023.101342 | - |
dc.identifier.bibliographicCitation | Cell Reports Medicine, v.5, no.1 | - |
dc.relation.isPartOf | Cell Reports Medicine | - |
dc.citation.title | Cell Reports Medicine | - |
dc.citation.volume | 5 | - |
dc.citation.number | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | bone tumor | - |
dc.subject.keywordAuthor | chondrosarcoma | - |
dc.subject.keywordAuthor | HIF-2α | - |
dc.subject.keywordAuthor | NAD<sup>+</sup> metabolism | - |
dc.subject.keywordAuthor | SIRT1 | - |
dc.subject.keywordAuthor | targeted therapy | - |