One of the key characteristics of cancer cells is their increased rate of glucose uptake and breakdown, a process known as glycolysis. Cancer cells utilize glycolysis as their main metabolic pathway to provide energy and, at the same time, sufficient nutrients to support rapid cell division and growth. The first step in glycolysis is catalyzed by hexokinase enzymes (HK), which phosphorylate glucose to glucose-6-phosphate (G6P). The most significant HK isoforms that catalyze this reaction are HK1 and HK2. HK1 is widely expressed in most normal adult tissue, whereas HK2 expression in normal tissue is limited1. In contrast, HK2 is overexpressed in many malignant cancer tissues that rely on glycolysis. Thus HK2 expression has a vital role in cancer metabolism.

While HK1 is sufficient for the metabolic requirements of normal cells, it cannot fulfill the greater metabolic demand of proliferating cancer cells2, 3. It was found that high HK2 levels correlate with poor disease prognosis4 and that high HK2 levels are required for oncogenic transformation despite the continuous expression of HK12. The high levels of HK2 in cancer tissue and its regulated association with the mitochondria, lend HK2 a specific role in cancer: funneling glucose both as a source of biomass building blocks and as a source of energy production, hence enabling cancer cells to rapidly grow and proliferate.

  1. Wilson JE (2003), J Exp Biol 206: 2049
  2. Patra KC et al (2013), Cancer Cell 24: 213
  3. Pedersen PL et al (2002), Biochim Biophys acta 1555: 14
  4. Peng S-Y et al (2007), Oncol Reports 19: 1045

back VDAC/HK2 Modulators