PXD004071-1

PXD004071 is an original dataset announced via ProteomeXchange.

Title	Targeting tumor mitochondrial metabolism overcomes resistance to antiangiogenics
Description	Epithelial malignancies are effectively treated by antiangiogenics; however, acquired resistance is a major problem in cancer therapeutics. Epithelial tumors commonly have mutations in the MAPK/Pi3K-AKT pathways, which leads to high-rate aerobic glycolysis. Here, we show how novel multikinase inhibitor antiangiogenics (TKIs) induce hypoxia correction in spontaneous breast and lung tumor models. When this happens, the tumors down-regulate glycolysis and switch to long-term reliance on mitochondrial respiration. A transcriptomic, metabolomic and phosphoproteomic study revealed that this metabolic switch is mediated by down-regulation of HIF1α and AKT and up-regulation of AMPK, allowing uptake and degradation of fatty acids and ketone bodies. The switch renders mitochondrial respiration necessary for tumor survival. Agents like phenformin or ME344 induce synergistic tumor control when combined with TKIs, especially in a sequential schedule, leading to metabolic synthetic lethality. Our study uncovers new mechanistic insights in the process of tumor resistance to TKIs, and may have clinical applicability
HostingRepository	PRIDE
AnnounceDate	2022-03-02
AnnouncementXML	Submission_2022-03-02_02:55:26.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Javier Munoz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-04-28 02:46:28	ID requested
⏵ 1	2022-03-02 02:55:26	announced
2	2024-10-22 05:34:55	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: angiogenesis, inhibitors, metabolism, mitochondria

Miguel Angel Quintela
contact affiliation	Spanish National Cancer Research Institute (CNIO)
contact email	mquintela@cnio.es
lab head
Javier Munoz
contact affiliation	CNIO
contact email	jmunozpe@cnio.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004071
     1. Label: PRIDE project
     2. Name: Targeting tumor mitochondrial metabolism overcomes resistance to antiangiogenics