PXD047420

PXD047420 is an original dataset announced via ProteomeXchange.

Title	Small molecule inhibitors of eIF4A1/2 impair the oxidative stress response in osteosarcoma cells to block tumor growth and metastatic capacity
Description	Effective therapies for metastatic osteosarcoma (OS) remain a major clinical unmet need. Targeting mRNA translation in metastatic OS represents an attractive option, as selective translation under stress supports the rapid synthesis of cytoprotective proteins that facilitate metastatic competence. We therefore assessed eukaryotic translation factors in OS, revealing high expression of eIF4A1 in metastatic OS. The eIF4A1 inhibitor, CR-1-31B, potently inhibited metastatic OS growth in vitro and reduced lung tumor burden in orthotopic mouse models. CR-1-31B synergized with the oxidative stress inducer, tert-butylhydroquinone (tBHQ), to enhance cell death under oxidative stress. Proteomic analysis revealed a subset of proteins that were upregulated by tBHQ alone, but inhibited by co-treatment of CR-1-31B, most notably the NRF2 antioxidant transcription factor, and NRF2 inactivation phenocopied CR-1-31B in blocking OS lung metastasis in vivo. Collectively, our data reveal that targeting eIF4A1 with CR-1-31B is highly effective in blocking OS metastasis by blunting the NRF2 antioxidant response.
HostingRepository	PRIDE
AnnounceDate	2024-07-16
AnnouncementXML	Submission_2024-07-16_13:26:55.039.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Hughes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-30 14:30:30	ID requested
⏵ 1	2024-07-16 13:26:55	announced

Dataset with its publication pending

submitter keyword: translation inhibitors, oxidative stress, rocaglates,osteosarcoma

Poul Sorensen
contact affiliation	Department of Molecular Oncology, BC Cancer
contact email	psorensen@bccrc.ca
lab head
Christopher Hughes
contact affiliation	BC Cancer Agency
contact email	chughes@bcgsc.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047420
     1. Label: PRIDE project
     2. Name: Small molecule inhibitors of eIF4A1/2 impair the oxidative stress response in osteosarcoma cells to block tumor growth and metastatic capacity