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PXD019998

PXD019998 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDeletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer
DescriptionActivation 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:34:53.797.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDavid Meierhofer
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-24 07:07:11ID requested
12023-01-05 06:13:17announced
22023-11-14 08:34:55announced2023-11-14: 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
Thorsten Cramer
contact affiliationDepartment of General, Visceral- and Transplantation Surgery, RWTH University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany
contact emailtcramer@ukaachen.de
lab head
David Meierhofer
contact affiliationMass Spectrometry Facility MPIMG
contact emailmeierhof@molgen.mpg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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