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NEOPLASIA 6: WARBURG EFFECT: Hallmark of CANCER. What, Why & How?

In this short tutorial, i have described an interesting Hallmark of Cancer- WARBURG EFFECT. You will learn the What, Why and How of This Effect. ***Follow me**** http://ilovepathology.com/ Twitter :   / vijaypatho     / ilovepathology2   Facebook:   / ilovepathology   Warburg effect in Cancer The major metabolic shift Reprogramming Energy Metabolism in the presence of adequate ocygen ATP is generated by Oxidative Phosphoryation As Oxygen Decreases Shift from Oxidative phosphorylation to Glycolysis- Anaerobic glycolysis PASTEUR EFFECT Otto Heinrich Warburg , German Physiologist Observed that cancer cells had increased rates of glycolysis Despite the availability of adequate oxygen levels- WARBURG EFFECT The puzzling questions Is this phenomenon Cancer specific? No! This is evident in rapidly growing normal tissues too as in embryonic tissue It is a property of growing cells but got “stuck” in cancer cells!! Why do cancer cells activate glycolysis despite the presence of oxygen? Assures ATP synthesis when tumor outgrows its oxygen supply The metabolic intermediates of AEROBIC GLYCOLYSIS provides raw material for the synthesis of cellular components in these rapidly dividing tumor cells! And also favor tumor growth Release of acid lowers extracellular pH which favors tumor invasion and suppresses immune effectors How do they manage to activate glycolysis despite the presence of oxygen? Induction of glycolytic enzymes BY overexpression of HIF 1 Induction of Pyruvate dehydrogenase kinase Down regulation of mitochondrial enzymes and decrease in the number of mitochondria Mitochondrial defects due to mutations in mitochondrial DNA leading to malfunction of oxidative phosphorylation Significance of understanding Warburg effect Diagnostic This property of “glucose hunger” is used in PET scanning of solid tumors 18F-flourodeoxyglucose, a nonmetabolizable glucose derivative of glucose is used where this is preferentially taken by tumor cells/rapidly dividing cells Therapeutic Numerous Glycolytic inhibitors have been developed which can be potential anticancer drugs Viewpoint! Warburg effect is a growth promoting metabolic alteration in cancer cells One of the Hallmarks of Cancer! lots of explanations are given for this effect. However the exact cause and its value,.. As of now still remains elusive!