PXD052718 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Glycosphingolipid synthesis mediates immune evasion in Kras-driven cancer |
Description | Cancer cells frequently alter their lipids to grow and adapt to their environment1–3. Despite the critical functions of lipid metabolism in membrane physiology, signaling, and energy production, how specific lipids contribute to tumorigenesis is incompletely understood. Here, using functional genomics and lipidomic approaches, we identified de novo sphingolipid synthesis as an essential pathway for cancer immune evasion. Synthesis of sphingolipids is surprisingly dispensable for cancer cell proliferation in culture or in immunodeficient mice but required for tumor growth in multiple syngeneic models. Blocking sphingolipid production in cancer cells enhances the anti-proliferative effects of natural killer (NK) and CD8+ T cells partly via interferon gamma (IFNg) signaling. Mechanistically, depletion of glycosphingolipids increases surface levels of IFNg receptor subunit 1 (Ifngr1), mediating IFNg-induced growth arrest and proinflammatory signaling. Finally, pharmacological inhibition of glycosphingolipid synthesis synergizes with checkpoint blockade therapy to enhance anti-tumor immune response. Altogether, our work identifies glycosphingolipids as necessary and limiting metabolites for cancer immune evasion. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-26 |
AnnouncementXML | Submission_2024-06-26_08:32:01.146.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | henrik molina |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-05-30 08:02:58 | ID requested | |
⏵ 1 | 2024-06-26 08:32:01 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Glycosphingolipid, Kras |
Contact List
kivanc birsoy |
contact affiliation | the rockefeller university |
contact email | kbirsoy@rockefeller.edu |
lab head | |
henrik molina |
contact affiliation | THE ROCKEFELLER UNIVERSITY |
contact email | henrik.molina@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052718
- Label: PRIDE project
- Name: Glycosphingolipid synthesis mediates immune evasion in Kras-driven cancer