The role of hexokinase in cancer

Abstract

A thorough understanding of the processes occurring in cancer cells is necessary to make cancer treatment as effective as possible. Changes in cellular metabolism in relation to normal cells are considered particularly important. One of the most interesting and promising areas is glucose metabolism and the factors affecting this process, with special emphasis on the potential role of hexokinases, especially the isoform II of this enzyme. Hexokinases (HK) are transferase enzymes involved in the process of glycolysis. Hexokinase II (HK II) plays an important role in initiating and maintaining the glycolysis process at a high level of efficiency, which is crucial for the growth and proliferation of cancer cells. An increase in the number of copies of the HK II gene and increased transcription of this enzyme resulting in the suppression of apoptosis and the enhancement of cell proliferation have been found in tumor cells. Hexokinase II also participates in the Crabtree effect by affecting the amount of ATP and thus the efficiency of the Ca2+ removal process outside the cell membrane by Ca2+ ATPase. Overexpression of HK II has thus far been found in pancreatic cancer, gastric cancer, breast cancer, squamous cell carcinoma of the larynx, glioblastoma multiforme, ovarian cancer and biliary tract cancer, indicating the possible key role of this enzyme in their formation and progression and providing the basis for seeking potential benefits of cancer treatment using HK II as a target of new drugs.