| Online-Ressource |
Verfasst von: | Scherr, Anna-Lena [VerfasserIn]  |
| Nader, Luisa [VerfasserIn]  |
| Xu, Kaiyu [VerfasserIn]  |
| Elssner, Christin [VerfasserIn]  |
| Ridder, Dirk A. [VerfasserIn]  |
| Nichetti, Federico [VerfasserIn]  |
| Mastel, Manuel [VerfasserIn]  |
| Fritzsche, Sarah [VerfasserIn]  |
| Kelmendi, Eblina [VerfasserIn]  |
| Schmitt, Nathalie [VerfasserIn]  |
| Hoffmeister-Wittmann, Paula [VerfasserIn]  |
| Hoffmeister-Wittmann, Paula [VerfasserIn]  |
| Weiler, Sofia Maria Elisabeth [VerfasserIn]  |
| Korell, Felix [VerfasserIn]  |
| Albrecht, Thomas [VerfasserIn]  |
| Schwab, Maximilian [VerfasserIn]  |
| Isele, Hanna [VerfasserIn]  |
| Kessler, Annika [VerfasserIn]  |
| Hüllein, Jennifer [VerfasserIn]  |
| Seretny, Agnieszka [VerfasserIn]  |
| Ye, Liangtao [VerfasserIn]  |
| Urbanik, Toni [VerfasserIn]  |
| Welte, Stefan [VerfasserIn]  |
| Leblond, Anne-Laure [VerfasserIn]  |
| Heilig, Christoph E. [VerfasserIn]  |
| Rahbari, Mohammad [VerfasserIn]  |
| Ali, Sheikh Adnan [VerfasserIn]  |
| Gallage, Suchira [VerfasserIn]  |
| Lenoir, Bénédicte [VerfasserIn]  |
| Wilhelm, Nina [VerfasserIn]  |
| Gärtner, Ulrike [VerfasserIn]  |
| Ogrodnik, Simon J. [VerfasserIn]  |
| Springfeld, Christoph [VerfasserIn]  |
| Tschaharganeh, Darjus-Felix [VerfasserIn]  |
| Fröhling, Stefan [VerfasserIn]  |
| Longerich, Thomas [VerfasserIn]  |
| Schulze-Bergkamen, Henning [VerfasserIn]  |
| Jäger, Dirk [VerfasserIn]  |
| Brandl, Lydia [VerfasserIn]  |
| Schirmacher, Peter [VerfasserIn]  |
| Straub, Beate Katharina [VerfasserIn]  |
| Weber, Achim [VerfasserIn]  |
| De Toni, Enrico N. [VerfasserIn]  |
| Goeppert, Benjamin [VerfasserIn]  |
| Heikenwalder, Mathias [VerfasserIn]  |
| Jackstadt, René-Filip [VerfasserIn]  |
| Rössler, Stephanie [VerfasserIn]  |
| Breuhahn, Kai [VerfasserIn]  |
| Köhler, Bruno Christian [VerfasserIn]  |
Titel: | Etiology-independent activation of the LTβ-LTβR-RELB axis drives aggressiveness and predicts poor prognosis in HCC |
Verf.angabe: | Anna-Lena Scherr, Luisa Nader, Kaiyu Xu, Christin Elssner, Dirk A. Ridder, Federico Nichetti, Manuel Mastel, Sarah Fritzsche, Eblina Kelmendi, Nathalie Schmitt, Paula Hoffmeister-Wittmann, Sofia M.E. Weiler, Felix Korell, Thomas Albrecht, Maximilian Schwab, Hanna Isele, Annika Kessler, Jennifer Hüllein, Agnieszka Seretny, Liangtao Ye, Toni Urbanik, Stefan Welte, Anne-Laure Leblond, Christoph E. Heilig, Mohammad Rahbari, Adnan Ali, Suchira Gallage, Bénédicte Lenoir, Nina Wilhelm, Ulrike Gärtner, Simon J. Ogrodnik, Christoph Springfeld, Darjus Tschaharganeh, Stefan Fröhling, Thomas Longerich, Henning Schulze-Bergkamen, Dirk Jäger, Lydia Brandl, Peter Schirmacher, Beate K. Straub, Achim Weber, Enrico N. De Toni, Benjamin Goeppert, Mathias Heikenwalder, Rene Jackstadt, Stephanie Roessler, Kai Breuhahn, Bruno C. Köhler |
E-Jahr: | 2024 |
Jahr: | August 2024 |
Umfang: | 17 S. |
Illustrationen: | Illustrationen |
Fussnoten: | Gesehen am 19.02.2024 |
Titel Quelle: | Enthalten in: Hepatology |
Ort Quelle: | [Alphen aan den Rijn] : Wolters Kluwer Health, 1981 |
Jahr Quelle: | 2024 |
Band/Heft Quelle: | 80(2024), 2, Seite 278-294 |
ISSN Quelle: | 1527-3350 |
Abstract: | Background and Aims: - HCC is the most common primary liver tumor, with an increasing incidence worldwide. HCC is a heterogeneous malignancy and usually develops in a chronically injured liver. The NF-κB signaling network consists of a canonical and a noncanonical branch. Activation of canonical NF-κB in HCC is documented. However, a functional and clinically relevant role of noncanonical NF-κB and its downstream effectors is not established. - Approach and Results: - Fur human HCC cohorts (total n = 1462) and 4 mouse HCC models were assessed for expression and localization of NF-κB signaling components and activating ligands. In vitro, NF-κB signaling, proliferation, and cell death were measured, proving a pro-proliferative role of v-rel avian reticuloendotheliosis viral oncogene homolog B (RELB) activated by means of NF-κB-inducing kinase. In vivo, lymphotoxin beta was identified as the predominant inducer of RELB activation. Importantly, hepatocyte-specific RELB knockout in a murine HCC model led to a lower incidence compared to controls and lower maximal tumor diameters. In silico, RELB activity and RELB-directed transcriptomics were validated on the The Cancer Genome Atlas HCC cohort using inferred protein activity and Gene Set Enrichment Analysis. In RELB-active HCC, pathways mediating proliferation were significantly activated. In contrast to v-rel avian reticuloendotheliosis viral oncogene homolog A, nuclear enrichment of noncanonical RELB expression identified patients with a poor prognosis in an etiology-independent manner. Moreover, RELB activation was associated with malignant features metastasis and recurrence. - Conclusions: - This study demonstrates a prognostically relevant, etiology-independent, and cross-species consistent activation of a lymphotoxin beta/LTβR/RELB axis in hepatocarcinogenesis. These observations may harbor broad implications for HCC, including possible clinical exploitation. Export |
DOI: | doi:10.1097/HEP.0000000000000657 |
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/10.1097/HEP.0000000000000657 |
| Volltext: https://journals.lww.com/hep/fulltext/9900/etiology_independent_activation_of_the.631.aspx |
| DOI: https://doi.org/10.1097/HEP.0000000000000657 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1881088928 |
Verknüpfungen: | → Zeitschrift |
Etiology-independent activation of the LTβ-LTβR-RELB axis drives aggressiveness and predicts poor prognosis in HCC / Scherr, Anna-Lena [VerfasserIn]; August 2024 (Online-Ressource)