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You are here: Home / Teams / Lotteau V - VIRIMI / Actualités / A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity

A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity

During liver carcinogenesis, the first enzyme of glycolysis GCK is replaced in hepatocytes by the hexokinase HK2. We show that it critically contributes to metabolic reprogramming and inhibition of innate immunity associated to liver cancer development.

A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity | Communications Biology (inist.fr)

Here we show that in hepatocellular carcinoma (HCC) tumors the highest expression level of hexokinase 2 (HK2) is inversely correlated to glucokinase (GCK) expression, and is associated to poor prognosis for patient survival. To further explore functional consequences of the GCK-to-HK2 isoenzyme switch occurring during carcinogenesis, HK2 was knocked-out in the HCC cell line Huh7 and replaced by GCK, to generate the Huh7-GCK+/HK2- cell line. HK2 knockdown and GCK expression rewired central carbon metabolism, stimulated mitochondrial respiration and restored essential metabolic functions of normal hepatocytes such as lipogenesis, VLDL secretion, glycogen storage. It also reactivated innate immune responses and sensitivity to natural killer cells, showing that consequences of the HK switch extend beyond metabolic reprogramming.