Hexokinase expression in liver preneoplasia and neoplasia

Mayer, Doris; Klimek, Fritz; Rempel, Annette; Bannasch, Peter

doi:10.1042/bst0250122

Cited by 31 publications

(16 citation statements)

References 5 publications

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“…During tumor development in tissues normally expressing HK-IV, gene expression of HK-II is induced whereas HK-IV is silenced. [24][25][26][27][28] This switch from a lower to a higher affinity HK subtype can provide a means to meet the high energy demand in tumors. Indeed, HK-II expression levels are closely associated with tumor grade and mortality in hepatocellular carcinoma.…”

Section: Hexokinase II In Metabolismmentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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Accumulating evidence reveals that metabolic and cell survival pathways are closely related, sharing common signaling molecules. Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis. Hexokinase II (HK-II) is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues. It is also upregulated in many types of tumors associated with enhanced aerobic glycolysis in tumor cells, the Warburg effect. In addition to the fundamental role in glycolysis, HK-II is increasingly recognized as a component of a survival signaling nexus. This review summarizes recent advances in understanding the protective role of HK-II, controlling cellular growth, preventing mitochondrial death pathway and enhancing autophagy, with a particular focus on the interaction between HK-II and Akt/mTOR pathway to integrate metabolic status with the control of cell survival.

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Section: Hexokinase II In Metabolismmentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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“…During this process, the expression of HK IV is silenced (Rempel et al, 1994b;Mathupala et al, 1997b;Mayer et al, 1997;Pedersen et al, 2002). This is clearly seen during tumorigenesis in the liver, where HK IV is expressed almost exclusively in adult hepatic tissue, whereas in highly malignant hepatomas HK IV is silenced and HK II, and to some extent HK I, are 'switched-on'.…”

Section: Hexokinase II Relative To Other Hexokinases (I Iii Iv) In mentioning

confidence: 80%

Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria

2006

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“…Consistently, HK2 and PKM2 isozymes are reported to be predominantly expressed in highly malignant tumours, and their functional role in promoting tumour progression has been demonstrated79. Particularly, a relative switch from HK4 (also named glucokinase) to HK2, and from PKL to PKM2 has been observed during progressive stages of liver transformation101112.…”

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confidence: 78%

PPARγ contributes to PKM2 and HK2 expression in fatty liver

et al. 2012

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Rapidly proliferating cells promote glycolysis in aerobic conditions, to increase growth rate. Expression of specific glycolytic enzymes, namely pyruvate kinase M2 and hexokinase 2, concurs to this metabolic adaptation, as their kinetics and intracellular localization favour biosynthetic processes required for cell proliferation. Intracellular factors regulating their selective expression remain largely unknown. Here we show that the peroxisome proliferator-activated receptor gamma transcription factor and nuclear hormone receptor contributes to selective pyruvate kinase M2 and hexokinase 2 gene expression in PTEN-null fatty liver. Peroxisome proliferator-activated receptor gamma expression, liver steatosis, shift to aerobic glycolysis and tumorigenesis are under the control of the Akt2 kinase in PTEN-null mouse livers. Peroxisome proliferator-activated receptor gamma binds to hexokinase 2 and pyruvate kinase M promoters to activate transcription. In vivo rescue of peroxisome proliferator-activated receptor gamma activity causes liver steatosis, hypertrophy and hyperplasia. Our data suggest that therapies with the insulin-sensitizing agents and peroxisome proliferator-activated receptor gamma agonists, thiazolidinediones, may have opposite outcomes depending on the nutritional or genetic origins of liver steatosis.

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Hexokinase expression in liver preneoplasia and neoplasia

Cited by 31 publications

References 5 publications

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria

PPARγ contributes to PKM2 and HK2 expression in fatty liver

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