Deletion of Lactate Dehydrogenase-A Impairs Oncogene-Induced Mouse Hepatocellular Carcinoma Development

Serra, Marina;Di Matteo, Mario;Serneels, Jens;Pal, Rajesh;Cafarello, Sarah Trusso;Lanza, Martina;Sanchez-Martin, Carlos;Evert, Matthias;Castegna, Alessandra;Calvisi, Diego Francesco;Mazzone, Massimiliano;Columbano, Amedeo

2022-01-01

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Abstract

Hepatocellular carcinoma (HCC) is a multistep process whereby abnormally proliferating cancer cells undergo extensive metabolic reprogramming. Metabolic alterations in hepatocarcinogenesis depend on the activation of specific oncogenes, thus partially explaining HCC heterogeneity. c-Myc oncogene overexpression, frequently observed in human HCCs, leads to a metabolic rewiring toward a Warburg phenotype and production of lactate, resulting in the acidification of the extracellular space, favoring the emergence of an immune-permissive tumor microenvironment. Here, we investigated whether Ldha genetic ablation interferes with metabolic reprogramming and HCC development in the mouse.