PXD039944 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: LC-MSMS,Liver, HCC, mouse, proteome, label free |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039944
- Label: PRIDE project
- Name: Liver epithelial cell-specific loss of mTOR aggravates tumor development in a murine model of nonalcoholic steatohepatitis related hepatocellular carcinoma