PXD020906 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Novel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas |
Description | Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematological diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quantitative nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing global protein levels changes, FADS2, a key enzyme regulating fatty acids synthesis, was found down-regulated after proteasome inhibition. Interestingly, SC26196, an inhibitor of FADS2, synergized with carfilzomib. Finally, to identify further combinational options, we performed high-throughput drug screening and uncovered novel drug interactions with carfilzomib. For instance, cyclosporin A, a known immunosuppressive agent, enhanced carfilzomib’s efficacy in vitro and in vivo. Altogether, these results demonstrate that carfilzomib and its combinations could be repurposed for LPS clinical management. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-07 |
AnnouncementXML | Submission_2024-10-07_13:34:58.924.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Dennis Kappei |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | 6x(13)C; 6x(13)C |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-08-14 02:45:14 | ID requested | |
⏵ 1 | 2024-10-07 13:34:59 | announced | |
Publication List
10.1007/s00018-020-03620-w; |
Jeitany M, Prabhu A, Dakle P, Pathak E, Madan V, Kanojia D, Mukundan V, Jiang YY, Landesman Y, Tam WL, Kappei D, Koeffler HP, Novel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas. Cell Mol Life Sci, 78(4):1837-1851(2021) [pubmed] |
Keyword List
submitter keyword: Carfilzomib, SILAC, quantitative mass spectrometry, Liposarcoma,Proteasome |
Contact List
Dennis Kappei |
contact affiliation | Cancer Science Institute of Singapore (CSI), National University of Singapore (NUS) |
contact email | dennis.kappei@nus.edu.sg |
lab head | |
Dennis Kappei |
contact affiliation | Cancer Science Institute of Singapore |
contact email | dennis.kappei@nus.edu.sg |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020906
- Label: PRIDE project
- Name: Novel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas