Alterations in metabolism and metabolic enzyme function and carcinogenesis

Abstract

Dr Otto Warburg (Nobel in 1931) in his lecture on Lindau Nobel Laureates Meeting in 1966, Germany, stated:

“Cancer, above all other diseases, has countless secondary causes… But, even for cancer, there is only one prime cause. To summarise in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar…”

Growth and development of organisms are strictly dependent from availability of nutrients. Evolved specific mechanisms controlling those processes can help organisms to survive starvation. Calorific restriction leads to longer life span, but the opposite, too many calories are associated with obesity and tumourigenesis. On a cellular level, normal dividing cells activate particular metabolic pathways to accumulate cell mass and energy for DNA synthesis required for reproduction. By contrast tumour cells reprogramme their metabolism, possibly in controlled way, for uncontrolled division and growth. Some genes encoding metabolic enzymes are inactivated while others exhibit increased expression, causing metabolic changes in tumour cells. Recent studies showed that certain glycolytic enzymes mainly active in cytoplasm may move from cytoplasm to the nucleus where they can play different, nonglycolytic functions e.g., control the gene expression. Therefore, to understand the influence of metabolism on gene expression can be crucial to discovering the causes of carcinogenesis.