دورية أكاديمية
Phosphoproteomics identify arachidonic-acid-regulated signal transduction pathways modulating macrophage functions with implications for ovarian cancer.
| العنوان: | Phosphoproteomics identify arachidonic-acid-regulated signal transduction pathways modulating macrophage functions with implications for ovarian cancer. |
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| المؤلفون: | Dietze R; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Hammoud MK; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Gómez-Serrano M; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Unger A; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Bieringer T; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany.; Present address: Hochschule Landshut, 84036 Landshut, Germany., Finkernagel F; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Sokol AM; Biomolecular Mass Spectrometry, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Nist A; Genomics Core Facility, Philipps University, Marburg, Germany., Stiewe T; Genomics Core Facility, Philipps University, Marburg, Germany., Reinartz S; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Ponath V; Institute for Tumor Immunology, Philipps University, Marburg, Germany., Preußer C; Institute for Tumor Immunology, Philipps University, Marburg, Germany., von Strandmann EP; Institute for Tumor Immunology, Philipps University, Marburg, Germany., Müller-Brüsselbach S; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany., Graumann J; Biomolecular Mass Spectrometry, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Müller R; Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany. |
| المصدر: | Theranostics [Theranostics] 2021 Jan 01; Vol. 11 (3), pp. 1377-1395. Date of Electronic Publication: 2021 Jan 01 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011- |
| مواضيع طبية MeSH: | Arachidonic Acid/*pharmacology , Macrophages/*drug effects , Ovarian Neoplasms/*drug therapy , Phosphorylation/*drug effects , Signal Transduction/*drug effects, Calcium/metabolism ; Extracellular Vesicles/drug effects ; Extracellular Vesicles/metabolism ; Female ; Group II Phospholipases A2/metabolism ; Humans ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/metabolism ; Ovarian Neoplasms/metabolism ; Reactive Oxygen Species/metabolism ; Transcription, Genetic/drug effects ; Tumor Microenvironment/drug effects |
| مستخلص: | Arachidonic acid (AA) is a polyunsaturated fatty acid present at high concentrations in the ovarian cancer (OC) microenvironment and associated with a poor clinical outcome. In the present study, we have unraveled a potential link between AA and macrophage functions. Methods: AA-triggered signal transduction was studied in primary monocyte-derived macrophages (MDMs) by phosphoproteomics, transcriptional profiling, measurement of intracellular Ca 2+ accumulation and reactive oxygen species production in conjunction with bioinformatic analyses. Functional effects were investigated by actin filament staining, quantification of macropinocytosis and analysis of extracellular vesicle release. Results: We identified the ASK1 - p38δ/α (MAPK13/14) axis as a central constituent of signal transduction pathways triggered by non-metabolized AA. This pathway was induced by the Ca 2+ -triggered activation of calmodulin kinase II, and to a minor extent by ROS generation in a subset of donors. Activated p38 in turn was linked to a transcriptional stress response associated with a poor relapse-free survival. Consistent with the phosphorylation of the p38 substrate HSP27 and the (de)phosphorylation of multiple regulators of Rho family GTPases, AA impaired actin filament organization and inhibited actin-driven macropinocytosis. AA also affected the phosphorylation of proteins regulating vesicle biogenesis, and consistently, AA enhanced the release of tetraspanin-containing exosome-like vesicles. Finally, we identified phospholipase A Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).) |
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| فهرسة مساهمة: | Keywords: arachidonic acid; macropinocytosis; ovarian cancer; phosphoproteomics |
| المشرفين على المادة: | 0 (Reactive Oxygen Species) 27YG812J1I (Arachidonic Acid) EC 3.1.1.4 (Group II Phospholipases A2) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20210104 Date Completed: 20210722 Latest Revision: 20210722 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7738879 |
| DOI: | 10.7150/thno.52442 |
| PMID: | 33391540 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1838-7640 |
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| DOI: | 10.7150/thno.52442 |