Quazi Tausif Ahmad
Post Graduation: AMU, Aligarh
Increase in aerobic glycolysis (Warburg Effect), a metabolic dysfunction, is causally linked to many epithelial cancers. Although the factor that trigger WE are not fully understood, some genetic factor such as induction of MYC oncogenic activation appears to one of the trigger. After MYC discovery, activation of the phosphoinositide 3-kinase (PI3K)/Akt), one of the most commonly deregulated pathways in cancer was found to regulate cell metabolism. In the last two decades almost all genetic mutations associated with cancer have been ascribed to activation metabolic programs that support tumor progression.
As a result of activation of WE, other metabolic processes of the cell are rewired. Since, most of the pyruvate converts to lactate; the Krebs cycle fuel is not available anymore. This results in recarboxylation of glutamine to alpha-KG to enter Krebs cycle. Also, as acetyl CoA is not abundant, lipogenesis occurs by alternate metabolic branch-points including carnitine shunt and glutaminolysis. These metabolic rewiring supports HIF stabilization and leads to accumulation of metabolites which has the ability to activate many oncogenic genes independently. In total, we thus promote tumor progression.