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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Golob-Schwarzl, N; Bettermann, K; Mehta, AK; Kessler, SM; Unterluggauer, J; Krassnig, S; Kojima, K; Chen, X; Hoshida, Y; Bardeesy, NM; Müller, H; Svendova, V; Schimek, MG; Diwoky, C; Lipfert, A; Mahajan, V; Stumptner, C; Thüringer, A; Fröhlich, LF; Stojakovic, T; Nilsson, KPR; Kolbe, T; Rülicke, T; Magin, TM; Strnad, P; Kiemer, AK; Moriggl, R; Haybaeck, J.
High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.
Transl Oncol. 2019; 12(2):256-268 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bettermann Kira
Diwoky Clemens
Fröhlich Leopold F.
Golob-Schwarzl Nicole
Haybäck Johannes
Kessler Sonja
Kraßnig Stefanie
Mahajan Vineet Sudheer
Mehta Anita Kuldeep
Müller Heimo
Schimek Michael G.
Stojakovic Tatjana
Stumptner Cornelia
Svendova Vendula
Unterluggauer Julia Judith
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Number of Figures: 9
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Abstract:
Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, and fibrosis at late stage. Disturbance of the keratin cytoskeleton and aggregation of keratins (KRTs) are essential for MDB formation. We analyzed livers of aged Krt18-/- mice that spontaneously developed in the majority of cases SH-associated HCC independent of sex. Interestingly, the hepatic lipid profile in Krt18-/- mice, which accumulate KRT8, closely resembles human SH lipid profiles and shows that the excess of KRT8 over KRT18 determines the likelihood to develop SH-associated HCC linked with enhanced lipogenesis. Our analysis of the genetic profile of Krt18-/- mice with 26 human hepatoma cell lines and with data sets of >300 patients with HCC, where Krt18-/- gene signatures matched human HCC. Interestingly, a high KRT8/18 ratio is associated with an aggressive HCC phenotype. We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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