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@ARTICLE{Crouchet:304510,
author = {E. Crouchet and E. Schaeffer and M. A. Oudot and J. Moehlin
and C. Gadenne and F. Jühling and H. El Saghire and N.
Fujiwara and S. Zhu and F. Akter Rasha and S. C. Durand and
A. Charlot and C. Ponsolles and R. Martin and N. Brignon and
F. Del Zompo and L. Meiss Heydmann and M. Parnot and N.
Hamdane and D. Heide$^*$ and J. Hetzer$^*$ and M.
Heikenwälder$^*$ and E. Felli and P. Pessaux and N. Pochet
and J. Zoll and B. Cunniff and Y. Hoshida and L. Mailly and
T. F. Baumert and C. Schuster},
title = {{T}argeting peroxiredoxin 2 prevents hepatocarcinogenesis
in metabolic liver disease models.},
journal = {The journal of clinical investigation},
volume = {135},
number = {21},
issn = {0021-9738},
address = {Ann Arbor, Mich.},
publisher = {ASCJ},
reportid = {DKFZ-2025-01898},
pages = {e169395},
year = {2025},
note = {2025 Sep 11;135(21):e169395},
abstract = {Treatment options for advanced liver disease and
hepatocellular carcinoma (HCC) are limited and strategies to
prevent HCC development are lacking. Aiming to discover
novel therapeutic targets, we combined genome wide
transcriptomic analysis of liver tissues from patients with
advanced liver disease and HCC and a cell-based system
predicting liver disease progression and HCC risk.
Computational analysis predicted peroxiredoxin 2 (PRDX2) as
a candidate gene mediating hepatocarcinogenesis and HCC
risk. Analysis of HCC patient tissues confirmed a perturbed
expression of PRDX2 in cancer. In vivo perturbation studies
in mouse models for MASH driven hepatocarcinogenesis showed
that specific Prdx2 knockout in hepatocytes significantly
improved metabolic liver functions, restored AMPK activity
and prevented HCC development by suppressing oncogenic
signaling. Perturbations studies in HCC cell lines, a CDX
mouse model and patient-derived HCC spheroids unraveled that
PRDX2 also mediates cancer initiation, cancer cell
proliferation and survival through its antioxidant activity.
Targeting PRDX2 may therefore be a valuable strategy to
prevent HCC development in metabolic liver disease.},
keywords = {Carbohydrate metabolism (Other) / Hepatology (Other) /
Oncology (Other) / Preventative medicine (Other) /
Therapeutics (Other)},
cin = {D440},
ddc = {610},
cid = {I:(DE-He78)D440-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40932790},
doi = {10.1172/JCI169395},
url = {https://inrepo02.dkfz.de/record/304510},
}