TY  - JOUR
A1  - Waidmann, Oliver
A1  - Pleli, Thomas
A1  - Weigert, Andreas
A1  - Imelmann, Esther
A1  - Kakoschky, Bianca
A1  - Schmithals, Jens Christian Johannes
A1  - Döring, Claudia
A1  - Frank, Matthias
A1  - Longerich, Thomas
A1  - Köberle, Verena
A1  - Hansmann, Martin-Leo
A1  - Brüne, Bernhard
A1  - Zeuzem, Stefan
A1  - Piiper, Albrecht
A1  - Đikić, Ivan
T1  - Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
T2  - Scientific reports
N2  - The nuclear factor kappa beta (NFκB) signaling pathway plays an important role in liver homeostasis and cancer development. Tax1-binding protein 1 (Tax1BP1) is a regulator of the NFκB signaling pathway, but its role in the liver and hepatocellular carcinoma (HCC) is presently unknown. Here we investigated the role of Tax1BP1 in liver cells and murine models of HCC and liver fibrosis. We applied the diethylnitrosamine (DEN) model of experimental hepatocarcinogenesis in Tax1BP1+/+ and Tax1BP1−/− mice. The amount and subsets of non-parenchymal liver cells in in Tax1BP1+/+ and Tax1BP1−/− mice were determined and activation of NFκB and stress induced signaling pathways were assessed. Differential expression of mRNA and miRNA was determined. Tax1BP1−/− mice showed increased numbers of inflammatory cells in the liver. Furthermore, a sustained activation of the NFκB signaling pathway was found in hepatocytes as well as increased transcription of proinflammatory cytokines in isolated Kupffer cells from Tax1BP1−/− mice. Several differentially expressed mRNAs and miRNAs in livers of Tax1BP1−/− mice were found, which are regulators of inflammation or are involved in cancer development or progression. Furthermore, Tax1BP1−/− mice developed more HCCs than their Tax1BP1+/+ littermates. We conclude that Tax1BP1 protects from liver cancer development by limiting proinflammatory signaling.
KW  - Cancer
KW  - Immunology
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76133
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-761334
SN  - 2045-2322
N1  - Open Access funding enabled and organized by Projekt DEAL. This work was supported by the “Patenschaftsmodell and the Nachwuchswissenschaftler Programm der Goethe-Universität Frankfurt”, Germany and in parts by the Deutsche Forschungsgemeinschaft (DFG), WA 2924/1-1.
VL  - 10
IS  - art. 16264
SP  - 1
EP  - 13
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -