High levels of the polyunsaturated fatty acid arachidonic acid (AA) in the ovarian carcinoma (OC) microenvironment are associated with short relapse-free survival. OC progression is also linked to impaired immunosurveillance, due in part to dysfunctional natural killer (NK) cells. In the present study, we have combined phosphoproteomics, transcriptional profiling and functional assays to study the impact of AA on NK cell functions. Our data show that AA (i) impairs interleukin-2-mediated NK cell proliferation and pro-inflammatory gene expression by blocking STAT1-dependent signaling, (ii) interferes with NK cell receptor (NCR) signaling, including inhibition of MICA-induced ERK phosphorylation and (iii) affects the production of reactive oxygen species. Intriguingly, low expression of several NK cell receptors is associated with a short survival of OC patients, suggesting that AA, dysfunction of NK cells and OC progression are functionally linked.
- Orbitrap 480
- TMT labelling
- FeNTA phospho-enrichment
- DDA
[doi:10.25345/C50G3H87N]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: TMT ; DDA ; phosphorylation ; Orbitrap 480
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Principal Investigators: (in alphabetical order) |
Prof. Dr. Rolf Mueller, Philipps-Universitaet Marburg, Zentrum fuer Tumorbiologie (Tumorbiologie) Institut fuer Molekularbiologie und Tumorforschung (IMT), Germany |
| Submitting User: | Wszymanski |
Hammoud MK, Meena C, Dietze R, Hoffmann N, Szymanski W, Finkernagel F, Nist A, Stiewe T, Graumann J, von Strandmann EP, Müller R.
Arachidonic acid impairs natural killer cell functions by disrupting signaling pathways driven by activating receptors and reactive oxygen species.
Cell Commun Signal. 2024 Nov 19;22(1):555. Epub 2024 Nov 19.
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