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Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Department of Medicine I, Lichtenberg Research Group for Molecular Hepatocarcinogenesis, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
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Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Cancers 2019, 11(8), 1053; https://doi.org/10.3390/cancers11081053
Received: 24 June 2019 / Revised: 19 July 2019 / Accepted: 23 July 2019 / Published: 25 July 2019
(This article belongs to the Special Issue NF-kappaB signalling pathway)
Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression in HCC is well documented. Pathway activation is significantly linked to poor prognostic traits as well as stemness characteristics, which places modulation of NF-κB signaling in the focus of therapeutic interventions. However, it is well recognized that the mechanistic importance of the pathway for HCC is highly context and cell type dependent. While constitutive pathway activation in an inflammatory etiological background can significantly promote HCC development and progression, absence of NF-κB signaling in differentiated liver cells also significantly enhances liver cancer development. Thus, therapeutic targeting of NF-κB as well as associated family members may not only exert beneficial effects but also negatively impact viability of healthy hepatocytes and/or cholangiocytes, respectively. The review presented here aims to decipher the complexity and paradoxical functions of NF-κB signaling in primary liver and non-parenchymal cells, as well as the induced molecular alterations that drive HCC development and progression with a particular focus on (immune-) therapeutic interventions. View Full-Text
Keywords: hepatocellular carcinoma; NF-κB signaling; hepatocarcinogenesis; chronic inflammation hepatocellular carcinoma; NF-κB signaling; hepatocarcinogenesis; chronic inflammation
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Czauderna, C.; Castven, D.; Mahn, F.L.; Marquardt, J.U. Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications. Cancers 2019, 11, 1053.

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