PXD019998 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer |
Description | Activation of the mechanistic target of rapamycin (mTOR) pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established liver epithelial cell (LEC)-specific knockout (KO) of mTOR (mTORLEC) mice. We used these mice to characterize the growth of colorectal liver metastases with or without partial hepatectomy to model different clinical settings. Although the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLEC mice compared with wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-ĸB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-ĸB in mTORLEC mice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in LECs. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage testing whether anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitors for cancer therapy. |
HostingRepository | PRIDE |
AnnounceDate | 2023-01-05 |
AnnouncementXML | Submission_2023-01-05_06:13:17.051.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | DavidMeierhofer |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-06-24 07:07:11 | ID requested | |
⏵ 1 | 2023-01-05 06:13:17 | announced | |
2 | 2023-11-14 08:34:55 | announced | 2023-11-14: Updated project metadata. |
Publication List
Jiao L, Eickhoff R, Egners A, Jumpertz S, Roth J, Erdem M, Kroh A, Duimel H, L, ó, pez-Iglesias C, Caro P, Heij LR, Schmeding M, Meierhofer D, Neumann UP, Cramer T, Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer. J Pathol, 255(3):270-284(2021) [pubmed] |
Keyword List
submitter keyword: liver metastasis,mTOR, NF-ĸB signaling |
Contact List
ThorstenCramer |
contact affiliation | Department of General, Visceral- and Transplantation Surgery, RWTH University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany |
contact email | tcramer@ukaachen.de |
lab head | |
DavidMeierhofer |
contact affiliation | Mass Spectrometry Facility MPIMG |
contact email | meierhof@molgen.mpg.de |
dataset submitter | |
Full Dataset Link List
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/2023/01/PXD019998 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019998
- Label: PRIDE project
- Name: Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer