Well-differentiated liver cancers reveal the potential link between ACE2 dysfunction and metabolic breakdown

Autor: Desquilles, Lise, Cano, Luis, Ghukasyan, Gevorg, Mouchet, Nicolas, Landreau, Clemence, Corlu, Anne, Clement, Bruno, Turlin, Bruno, Desert, Romain, Musso, Orlando
Přispěvatelé: Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Inserm Institut National de la Sante et de la Recherche Medicale (Inserm) European Commission, Univ Rennes 1, Ministere de l'Enseignement Superieur, Institut National du Cancer Institut National du Cancer (INCA) France [INCA_12688], Ligue Nationale Contre le Cancer 2018, Comites d'Ille-et-Vilaine et Vendee, HAL UR1, Admin
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports
Scientific Reports, 2022, 12 (1), pp.1859. ⟨10.1038/s41598-021-03710-0⟩
Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
ISSN: 2045-2322
DOI: 10.1038/s41598-021-03710-0⟩
Popis: International audience; Angiotensin-converting enzyme 2 (ACE2) is the receptor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing Coronavirus disease 2019 (COVID-19). Transmembrane serine protease 2 (TMPRSS2) is a coreceptor. Abnormal hepatic function in COVID-19 suggests specific or bystander liver disease. Because liver cancer cells express the ACE2 viral receptor, they are widely used as models of SARS-CoV-2 infection in vitro. Therefore, the purpose of this study was to analyze ACE2 and TMPRSS2 expression and localization in human liver cancers and in non-tumor livers. We studied ACE2 and TMPRSS2 in transcriptomic datasets totaling 1503 liver cancers, followed by high-resolution confocal multiplex immunohistochemistry and quantitative image analysis of a 41-HCC tissue microarray. In cancers, we detected ACE2 and TMPRSS2 at the biliary pole of tumor hepatocytes. In whole mount sections of five normal liver samples, we identified ACE2 in hepatocyte's bile canaliculi, biliary epithelium, sinusoidal and capillary endothelial cells. Tumors carrying mutated beta-catenin showed ACE2 DNA hypomethylation and higher mRNA and protein expression, consistently with predicted beta-catenin response sites in the ACE2 promoter. Finally, ACE2 and TMPRSS2 co-expression networks highlighted hepatocyte-specific functions, oxidative stress and inflammation, suggesting a link between inflammation, ACE2 dysfunction and metabolic breakdown.
Databáze: OpenAIRE
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