PXD058998

PXD058998 is an original dataset announced via ProteomeXchange.

Title	FAK modulates glioblastoma stem cell energetics via actomyosin contractility: regulation of glycolysis and mitochondrial function
Description	Glycolysis and the TCA cycle are commonly reprogrammed to fulfil the bioenergetic and biosynthetic demands of cancer cells. Although the extracellular matrix is known to influence glycolysis and the TCA cycle, it is not well understood how specific adhesion proteins and their downstream effectors contribute to metabolic changes and to the mitigation of metabolic stress. Here, we report that the canonical focal adhesion protein FAK is required for optimal cellular energetics through both glycolysis and the TCA cycle in a transformed neural stem cell model of glioblastoma. Mechanistically, FAK promotes the TCA cycle by keeping myosin II activity low in cells with a mesenchymal-like morphology. Genetic deletion of FAK induces an epithelial-like morphology with elevated myosin II activity as evidenced by phospho-myosin light chain accumulation at cell-cell contacts. In this context these cells have impaired glycolysis and TCA cycle flux that is accompanied by shortening of mitochondria fragments. Treating FAK depleted cells with multiple Rho-kinase (ROCK) inhibitors restores efficient TCA cycle flux, mitochondrial morphology, cells’ mesenchymal nature and viability. Phenotypically, the reduction in cell energetics after FAK depletion is accompanied by reduced cancer cell motility and invasiveness in vitro and suppression of tumour growth and increased survival in an orthotopic murine model. We demonstrate a novel role for FAK as an adhesion protein which can modulate cellular energetics and mitochondria morphology in glioblastoma stem cells with profound consequences for cancer-associated cell phenotypes and tumour growth in vivo.
HostingRepository	PRIDE
AnnounceDate	2025-12-15
AnnouncementXML	Submission_2025-12-14_16:21:21.357.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von Kriegsheim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-18 08:12:04	ID requested
⏵ 1	2025-12-14 16:21:22	announced

10.1242/dmm.052634;

Masalmeh RHA, Dawson JC, Garcia VA, Muir MT, Carter RN, Hardingham GE, Davies C, Graham R, von Kriegsheim A, Marques J, Pednekar C, Pollard SM, Carragher NO, Brunton VG, Frame MC, FAK modulates glioblastoma stem cell energetics via regulation of glycolysis and glutamine oxidation. Dis Model Mech, 18(11):(2025) [pubmed]

submitter keyword: FAK, metabolims

Alex von Kriegsheim
contact affiliation	u o edinburgh
contact email	avonkri@ed.ac.uk
lab head
Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ed.ac.uk
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/2025/12/PXD058998

PRIDE project URI

• PRIDE
  1. PXD058998
     1. Label: PRIDE project
     2. Name: FAK modulates glioblastoma stem cell energetics via actomyosin contractility: regulation of glycolysis and mitochondrial function