PXD051172
PXD051172 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Phosphoproteomics reveals selective induction of signal transduction pathways by different lysophosphatidic acid species in macrophages |
| Description | Lysophosphatidic acid (LPA) species, prevalent in the tumor microenvironment (TME), adversely impact various cancers. In ovarian cancer, the 18:0 and 20:4 LPA species in particular are associated with shorter relapse-free survival, indicating distinct effects on cellular signaling networks. Macrophages represent a cell type of high relevance in the TME, but the impact of LPA on them remains obscure. Here, we uncovered distinct LPA-species-specific responses in human monocyte-derived macrophages through unbiased phosphoproteomics, with 87 and 161 phosphosites upregulated by 20:4 and 18:0 LPA, respectively, and only 24 shared sites. Specificity was even more pronounced for downregulated phosphosites (163 versus 5 sites). Considering the frequently high levels of 20:4 LPA in the TME and its association with poor survival, these findings are of relevance for further understanding of cancer promotion and maintenance. Pathway analysis pinpointed RHO/RAC1 GTPase signaling as the predominantly impacted pathway, including AHRGEF and DOCK guanine exchange factors, ARHGAP GTPase activating proteins, and regulatory protein kinases. Consistent with these findings, exposure to 20:4 resulted in strong alterations to the actin filament network and a consequent enhancement of macrophage migration. Moreover, 20:4 LPA induced p38 phosphorylation, a response not mirrored by 20:4 LPA, whereas the pattern for AKT was reversed. Furthermore, RNA profiling identified genes involved in cholesterol/lipid metabolism as selective targets of 20:4 LPA. These findings imply that the two LPA species cooperatively regulate different pathways to support functions essential for pro-tumorigenic macrophages within the TME. These include cellular survival via AKT activation and migration through RHO/RAC1 and p38 signaling. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-05-13 |
| AnnouncementXML | Submission_2024-05-13_01:21:20.184.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Witold Szymanski |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Phospho |
| Instrument | Orbitrap Exploris 480 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-04-03 02:56:18 | ID requested | |
| ⏵ 1 | 2024-05-13 01:21:20 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Exploris , Phosphorylation, Orbitrap, macrophages, lysophosphatidic acid |
Contact List
| Prof. Dr. Rolf Mueller | |
|---|---|
| contact affiliation | Philipps-Universitaet Marburg, Zentrum fuer Tumorbiologie (Tumorbiologie) Institut fuer Molekularbiologie und Tumorforschung (IMT) |
| contact email | rmueller@imt.uni-marburg.de |
| lab head | |
| Witold Szymanski | |
| contact affiliation | Philipps-University Marburg Biochemical/Pharmacological Center Department of Medicine |
| contact email | witold.szymanski@uni-marburg.de |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v07/MSV000094459/ |
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