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Verfasst von:Scherr, Anna-Lena [VerfasserIn]   i
 Nader, Luisa [VerfasserIn]   i
 Xu, Kaiyu [VerfasserIn]   i
 Elssner, Christin [VerfasserIn]   i
 Ridder, Dirk A. [VerfasserIn]   i
 Nichetti, Federico [VerfasserIn]   i
 Mastel, Manuel [VerfasserIn]   i
 Fritzsche, Sarah [VerfasserIn]   i
 Kelmendi, Eblina [VerfasserIn]   i
 Schmitt, Nathalie [VerfasserIn]   i
 Hoffmeister-Wittmann, Paula [VerfasserIn]   i
 Hoffmeister-Wittmann, Paula [VerfasserIn]   i
 Weiler, Sofia Maria Elisabeth [VerfasserIn]   i
 Korell, Felix [VerfasserIn]   i
 Albrecht, Thomas [VerfasserIn]   i
 Schwab, Maximilian [VerfasserIn]   i
 Isele, Hanna [VerfasserIn]   i
 Kessler, Annika [VerfasserIn]   i
 Hüllein, Jennifer [VerfasserIn]   i
 Seretny, Agnieszka [VerfasserIn]   i
 Ye, Liangtao [VerfasserIn]   i
 Urbanik, Toni [VerfasserIn]   i
 Welte, Stefan [VerfasserIn]   i
 Leblond, Anne-Laure [VerfasserIn]   i
 Heilig, Christoph E. [VerfasserIn]   i
 Rahbari, Mohammad [VerfasserIn]   i
 Ali, Sheikh Adnan [VerfasserIn]   i
 Gallage, Suchira [VerfasserIn]   i
 Lenoir, Bénédicte [VerfasserIn]   i
 Wilhelm, Nina [VerfasserIn]   i
 Gärtner, Ulrike [VerfasserIn]   i
 Ogrodnik, Simon J. [VerfasserIn]   i
 Springfeld, Christoph [VerfasserIn]   i
 Tschaharganeh, Darjus-Felix [VerfasserIn]   i
 Fröhling, Stefan [VerfasserIn]   i
 Longerich, Thomas [VerfasserIn]   i
 Schulze-Bergkamen, Henning [VerfasserIn]   i
 Jäger, Dirk [VerfasserIn]   i
 Brandl, Lydia [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Straub, Beate Katharina [VerfasserIn]   i
 Weber, Achim [VerfasserIn]   i
 De Toni, Enrico N. [VerfasserIn]   i
 Goeppert, Benjamin [VerfasserIn]   i
 Heikenwalder, Mathias [VerfasserIn]   i
 Jackstadt, René-Filip [VerfasserIn]   i
 Rössler, Stephanie [VerfasserIn]   i
 Breuhahn, Kai [VerfasserIn]   i
 Köhler, Bruno Christian [VerfasserIn]   i
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

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