The Mechanisms of Regulation of Aerobic Glycolysis (Warburg Effect) by Oncoproteins in Carcinogenesis

AbstractAccording to modern concepts, tumor formation is associated with impairments in the structure of protooncogenes and/or deactivation of suppressor genes, regardless of the nature of carcinogenic factor. As a consequence, unregulated onco-proteins activate extracellular proteases, resulting in the destruction of the extracellular matrix, which facilitates cell invasion, deterioration of the cell-cell contacts, and metastasis. Tumor development requires activation of certain transcription factors; however, many oncoproteins are not transcription factors. It can be assumed that these oncoproteins are not the ultimate effectors of tumor development, but rather transmitters of the carcinogenic signal to the transcription factors promoting tumorigenesis. Here, we describe the mechanisms of carcinogenesis caused by various oncogenes/oncoproteins. We conclude that the common feature of these mechanisms is stimulation of aerobic glycolysis (Warburg effect) regulated, as a rule, through the activation of the HIF α transcription factor. The role of aerobic glycolysis at the early stages of carcinogenesis is discussed.
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research