PXD049304-1

PXD049304 is an original dataset announced via ProteomeXchange.

Title	Inhibition of Acyl-CoA Synthetase Long Chain (ACSL) Isozymes Decreases Multiple Myeloma Cell Proliferation, Mitochondrial Function and Affects Key Survival Pathways
Description	Multiple myeloma (MM) is an incurable cancer of plasma cells that will cause ~12,590 deaths in the USA in 2023. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression but the underlying mechanisms remain unknown. The acyl-CoA synthetase long-chain family members (ACSLs) convert free long-chain fatty acids into fatty acyl-CoA esters, and play a key role in catabolic and anabolic fatty acid metabolism. Cancer Dependency Map data suggested that ACSL4 and ACSL3 are among the top 25% Hallmark Fatty Acid Metabolism genes that support MM fitness. Here, we show inhibition of the ACSLs in human myeloma cell lines using the pharmacological inhibitor Triascin C (TriC) caused apoptosis, and decreased proliferation in a dose- and time-dependent manner. As KRAS mutants are the most common mutation among MM patients, we used MM.1S cells to study the mechanisms of TriC toxicity. RNA-seq of MM.1S cells treated with TriC for 24 hours had transcriptomes significantly enriched in apoptosis, ferroptosis, and ER stress. Proteomics of MM.1S cells treated with TriC for 48 hours revealed that mitochondrial dysfunction and oxidative phosphorylation were significantly enriched pathways of interest. Indeed, metabolic flux analysis showed MM.1S cells treated with TriC after 24 hours had decreased mitochondrial ATP production rates. Flow cytometric analyses revealed decreases in mitochondrial number and membrane potential with increased mitochondrial superoxide levels. Implications: Overall, our data support the hypothesis that suppression of ACSL in human MM cells inhibited their growth and viability, potentially indicating that ACSL proteins may be promising therapeutic targets in treating myeloma progression.
HostingRepository	PRIDE
AnnounceDate	2025-06-16
AnnouncementXML	Submission_2025-06-15_16:35:02.398.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carlos Gartner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-09 08:08:12	ID requested
⏵ 1	2025-06-15 16:35:03	announced

Murphy CS, Fairfield H, DeMambro VE, Fadel S, Gartner CA, Karam M, Potts C, Rodriguez P, Qiang YW, Hamidi H, Guan X, Vary CPH, Reagan MR, Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction. Mol Oncol, 19(6):1687-1706(2025) [pubmed]

10.1002/1878-0261.13794;

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Triacsin C, ACSL, Multiple Myeloma, MM.1S,Acyl-CoA Synthetase Long Chain, Fatty acid metabolism

Calvin Vary
contact affiliation	Maine Medical Center Research Institute 81 Research Dr. Scarborough, ME 04074
contact email	Calvin.Vary@mainehealth.org
lab head
Carlos Gartner
contact affiliation	MaineHealth Institute for Research
contact email	gusti.gartner@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/06/PXD049304

PRIDE project URI

• PRIDE
  1. PXD049304
     1. Label: PRIDE project
     2. Name: Inhibition of Acyl-CoA Synthetase Long Chain (ACSL) Isozymes Decreases Multiple Myeloma Cell Proliferation, Mitochondrial Function and Affects Key Survival Pathways