PXD039944

PXD039944 is an original dataset announced via ProteomeXchange.

Title	Liver epithelial cell-specific loss of mTOR aggravates tumor development in a murine model of nonalcoholic steatohepatitis related hepatocellular carcinoma
Description	Due to the global obesity epidemic the incidences of nonalcoholic steatohepatitis (NASH) and NASH-related hepatocellular carcinoma (HCC) are on the rise. Non-invasive treatment options for HCC are scarce and innovative therapy regimes are urgently needed. The mechanistic target of rapamycin (mTOR) is of fundamental importance for the regulation of cellular metabolism and mTOR pathway activation is frequently observed in HCCs. However, mTOR inhibition failed to benefit the clinical course of HCC patients, demonstrating the need for a better understanding of the molecular and functional consequences of blocking mTOR signaling in primary liver cancer. To address this, we established a tumor cell-specific inactivation of mTOR in a murine model of non-alcoholic steatohepatitis (NASH)-driven HCC. After 30 weeks of diet, tumor, and liver volumes as well as whole body fat percentage were evaluated by non-invasive in vivo micro-computed tomography (µCT), and livers were collected for subsequent analyses. Unexpectedly, the tumor load exploded in mTORLEC livers and knock-out mice showed improved glucose tolerance among other signs of major metabolic alterations. Detailed proteome analysis indicated extensive changes in arachidonic and bile acid metabolism in the liver. The simulation of metformin intervention via kinetic modeling predicted the existence of a therapeutic window, in which the drug selectively targets mTORLEC HCC tissue.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:29.399.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Preisinger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-08 02:06:50	ID requested
1	2023-11-15 06:39:30	announced
⏵ 2	2024-10-22 06:14:29	announced	2024-10-22: Updated project metadata.

10.1016/J.NEO.2023.100945;

submitter keyword: LC-MSMS,Liver, HCC, mouse, proteome, label free

Andreas Kroh
contact affiliation	Department of General, Visceral and Transplantation Surgery, University Clinic RWTH Aachen, Aachen, Germany
contact email	akroh@ukaachen.de
lab head
Christian Preisinger
contact affiliation	Proteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact email	cpreisinger@ukaachen.de
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/2023/11/PXD039944

PRIDE project URI

• PRIDE
  1. PXD039944
     1. Label: PRIDE project
     2. Name: Liver epithelial cell-specific loss of mTOR aggravates tumor development in a murine model of nonalcoholic steatohepatitis related hepatocellular carcinoma