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| Verfasst von: | Konopa, Andreas [VerfasserIn]  |
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| | Meier, Melanie A. [VerfasserIn] |
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| | Franz, Miriam J. [VerfasserIn] |
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| | Bernardinelli, Emanuele [VerfasserIn] |
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| | Voegele, Anna-Lena [VerfasserIn] |
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| | Atreya, Raja [VerfasserIn] |
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| | Ribback, Silvia [VerfasserIn] |
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| | Rössler, Stephanie [VerfasserIn] |
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| | Aigner, Achim [VerfasserIn] |
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| | Singer, Kerstin [VerfasserIn] |
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| | Singer, Stephan [VerfasserIn] |
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| | Sarikas, Antonio [VerfasserIn] |
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| | Muehlich, Susanne [VerfasserIn] |
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| Titel: | LPA receptor 1 (LPAR1) is a novel interaction partner of Filamin A that promotes Filamin A phosphorylation, MRTF-A transcriptional activity and oncogene-induced senescence |
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| Verf.angabe: | Andreas Konopa, Melanie A. Meier, Miriam J. Franz, Emanuele Bernardinelli, Anna-Lena Voegele, Raja Atreya, Silvia Ribback, Stephanie Roessler, Achim Aigner, Kerstin Singer, Stephan Singer, Antonio Sarikas and Susanne Muehlich |
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| E-Jahr: | 2022 |
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| Jahr: | 28 December 2022 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 31.01.2023 |
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| Titel Quelle: | Enthalten in: Oncogenesis |
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| Ort Quelle: | [Erscheinungsort nicht ermittelbar] : Nature Publ., 2012 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 11(2022) vom: Dez., Artikel-ID 69, Seite 1-12 |
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| ISSN Quelle: | 2157-9024 |
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| Abstract: | Myocardin-related transcription factors A and B (MRTFs) are coactivators of Serum Response Factor (SRF), which controls fundamental biological processes such as cell growth, migration, and differentiation. MRTF and SRF transcriptional activity play an important role in hepatocellular carcinoma (HCC) growth, which represents the second leading cause of cancer-related mortality in humans worldwide. We, therefore, searched for druggable targets in HCC that regulate MRTF/SRF transcriptional activity and can be exploited therapeutically for HCC therapy. We identified the G protein-coupled lysophosphatidic acid receptor 1 (LPAR1) as a novel interaction partner of MRTF-A and Filamin A (FLNA) using fluorescence resonance energy transfer-(FRET) and proximity ligation assay (PLA) in vitro in HCC cells and in vivo in organoids. We found that LPAR1 promotes FLNA phosphorylation at S2152 which enhances the complex formation of FLNA and MRTF-A, actin polymerization, and MRTF transcriptional activity. Pharmacological blockade or depletion of LPAR1 prevents FLNA phosphorylation and complex formation with MRTF-A, resulting in reduced MRTF/SRF target gene expression and oncogene-induced senescence. Thus, inhibition of the LPAR1-FLNA-MRTF-A interaction represents a promising strategy for HCC therapy. |
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| DOI: | doi:10.1038/s41389-022-00445-z |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1038/s41389-022-00445-z |
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| | Volltext: https://www.nature.com/articles/s41389-022-00445-z |
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| | DOI: https://doi.org/10.1038/s41389-022-00445-z |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Liver cancer |
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| | Target identification |
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| K10plus-PPN: | 1832785726 |
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| Verknüpfungen: | → Zeitschrift |
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LPA receptor 1 (LPAR1) is a novel interaction partner of Filamin A that promotes Filamin A phosphorylation, MRTF-A transcriptional activity and oncogene-induced senescence / Konopa, Andreas [VerfasserIn]; 28 December 2022 (Online-Ressource)
