Autor segons l'article: Fekry B; Ribas-Latre A; Baumgartner C; Mohamed A; Kolonin M; Sladek F; Younes M; Eckel-Mahan K
Departament: Medicina i Cirurgia
Autor/s de la URV: Ribas Latre, Aleix
Resum: ©©2019 American Association for Cancer Research. The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide. Although the incidence of HCC in males is considerably higher than in females, the projected rates of HCC incidence are increasing for both sexes. A recently appreciated risk factor for HCC is the growing problem of nonalcoholic fatty liver disease, which is usually associated with obesity and the metabolic syndrome. In this study, we showed that under conditions of fatty liver, female mice were more likely to develop HCC than expected from previous models. Using an inducible knockout model of the tumor-suppressive isoform of hepatocyte nuclear factor 4 alpha (P1-HNF4α) in the liver in combination with prolonged high fat (HF) diet, we found that HCC developed equally in male and female mice as early as 38 weeks of age. Similar sex-independent HCC occurred in the STAM model of mice, in which severe hyperglycemia and HF feeding results in rapid hepatic lipid deposition, fibrosis, and ultimately HCC. In both sexes, reduced P1-HNF4α activity, which also occurs under chronic HF diet feeding, increased hepatic lipid deposition and produced a greatly augmented circadian rhythm in IL6, a factor previously linked with higher HCC incidence in males. Loss of HNF4α combined with HF feeding induced epithelial–mesenchymal transition in an IL6-dependent manner. Collectively, these data provide a mechanism-based working hypothesis that could explain the rising incidence of aggressive HCC. Significance: This study provides a mechanism for the growing incidence of hepatocellular carcinoma in both men and women, which is linked to nonalcoholic fatty liver disease.
Àrees temàtiques: Astronomia / física Biotecnología Cancer research Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Farmacia General medicine Interdisciplinar Medicina i Medicina ii Medicina iii Medicina veterinaria Odontología Oncology Química Saúde coletiva
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: aleix.ribas@urv.cat
Data d'alta del registre: 2023-02-19
Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
Enllaç font original: https://aacrjournals.org/cancerres/article/79/22/5860/638347/HNF4-Deficient-Fatty-Liver-Provides-a-Permissive
Referència a l'article segons font original: Cancer Research. 79 (22): 5860-5873
Referència de l'ítem segons les normes APA: Fekry B; Ribas-Latre A; Baumgartner C; Mohamed A; Kolonin M; Sladek F; Younes M; Eckel-Mahan K (2019). HNF4a-deficient fatty liver provides a permissive environment for sex-independent hepatocellular carcinoma. Cancer Research, 79(22), 5860-5873. DOI: 10.1158/0008-5472.CAN-19-1277
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
DOI de l'article: 10.1158/0008-5472.CAN-19-1277
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2019
Tipus de publicació: Journal Publications