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.

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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!

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