PXD022723

PXD022723 is an original dataset announced via ProteomeXchange.

Title	Fasting reverses drug-resistance in hepatocellular carcinoma through p53-dependent metabolic synergism
Description	Cancer cells voraciously consume nutrients to support their growth, exposing a metabolic vulnerability that can be therapeutically exploited. Here we show in hepatocellular carcinoma (HCC) cells, xenografts, and in patient-derived HCC organoids that fasting can synergistically sensitise resistant HCC to sorafenib. Mechanistically, sorafenib acts non-canonically as inhibitor of mitochondrial respiration, causing resistant cells to depend on glycolysis for survival. Fasting, through reduction in glucose and impeded AKT/mTOR-signalling, prevents this Warburg shift. p53 is necessary and sufficient for the sorafenib-sensitizing effect of nutrient restriction and crucial for improvement of sorafenib efficacy through intermittent fasting (IF) in an orthotopic HCC mouse model. Together, our data indicate IF and sorafenib as clinically actionable, rational combination therapy for HCC with intact p53 signalling. As HCC therapy is currently severely limited by resistance, these results should instigate clinical studies with the goal of improving therapy response in advanced-stage, and possibly even early-stage, HCC.
HostingRepository	PRIDE
AnnounceDate	2022-05-27
AnnouncementXML	Submission_2022-05-27_07:17:19.699.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Galhuber
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-25 03:38:53	ID requested
⏵ 1	2022-05-27 07:17:21	announced

Krstic J, Reinisch I, Schindlmaier K, Galhuber M, Riahi Z, Berger N, Kupper N, Moyschewitz E, Auer M, Michenthaler H, N, ö, ssing C, Depaoli MR, Ramadani-Muja J, Usluer S, Stryeck S, Pichler M, Rinner B, Deutsch AJA, Reinisch A, Madl T, Chiozzi RZ, Heck AJR, Huch M, Malli R, Prokesch A, Fasting improves therapeutic response in hepatocellular carcinoma through p53-dependent metabolic synergism. Sci Adv, 8(3):eabh2635(2022) [pubmed]

ProteomeXchange project tag: EPIC-XS

submitter keyword: TP53, HCC, HepG2, xenografts, sorafenib, starvation

Andreas Prokesch
contact affiliation	Gottfried Schatz Research Center for Cell Signaling, Metabolism & Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, 8010 Graz, Austria
contact email	andreas.prokesch@medunigraz.at
lab head
Markus Galhuber
contact affiliation	Medical University of Graz
contact email	markus.galhuber@medunigraz.at
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/2022/02/PXD022723

PRIDE project URI

• PRIDE
  1. PXD022723
     1. Label: PRIDE project
     2. Name: Fasting reverses drug-resistance in hepatocellular carcinoma through p53-dependent metabolic synergism