PXD020906-1

PXD020906 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-14 02:45:14	ID requested
⏵ 1	2024-10-07 13:34:59	announced

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]

submitter keyword: Carfilzomib, SILAC, quantitative mass spectrometry, Liposarcoma,Proteasome

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

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PRIDE project URI

• PRIDE
  1. PXD020906
     1. Label: PRIDE project
     2. Name: Novel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas