NL repository
menu
검색
Library
Browse
Communities & Collections
By Date
Authors
Titles
Subject
My Repository
My Account
Receive email updates
Edit Profile
DSpace at EWHA
의과대학
의학과
Journal papers
View : 152 Download: 0
Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis
Title
Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis
Authors
Suh
;
Jooyeon
;
Kim
;
Hyeonkyeong
;
Min
;
Jiyun
;
Yeon
;
Hyun Ju
;
Hemberg
;
Martin
;
Scimeca
;
Luca
;
Wu
;
Ming-Ru
;
Kang
;
Hyun Guy
;
Yi-Jun
;
Jin-Hong
Ewha Authors
김이준
SCOPUS Author ID
김이준
Issue Date
2024
Journal Title
Cell Reports Medicine
ISSN
2666-3791
Citation
Cell Reports Medicine vol. 5, no. 1
Keywords
bone tumor
;
chondrosarcoma
;
HIF-2α
;
NAD<sup>+</sup>
;
metabolism
;
SIRT1
;
targeted therapy
Publisher
Cell Press
Indexed
SCIE; SCOPUS
Document Type
Article
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)
DOI
10.1016/j.xcrm.2023.101342
Appears in Collections:
의과대학
>
의학과
>
Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML
Show full item record
Find@EWHA
트윗하기
BROWSE
Communities & Collections
By Date
Authors
Titles
Subject