一个关健调控点是
pyruvate
Cancers tend to have
- selective expression of PKM2 (instead of PKM1), causing return to FETAL phenotype.
[step: phosphoenolpyruvate -->pyruvate]
- inactivation of PDC (pyruvate dehydrogenase complex): basis for the controversial canadian DCA cancer therapy in that DCA inhibits PDH kinase by irreversible binding to the pyruvate site, which results in the re-activation of PDC, and eventual restoration of aerobic respiration, proper mitochondrial function hence apoptosis.
[step: pyruvate --> acetyl CoA]
- high expression of transcription factor HIF (hypoxia inducible factor): the expression of enzymes for both above steps, and many other key players, such as Glut-1 (gluocose transporter), VEGF and some MMPs/cathepsin, are regulated by HIF. I am sure you are familiar with avastin
glucose surge => enhanced tumor anaerobic metabolism => hypoxia => HIF => expression of cancer growth, angiogenesis, metastasis related proteins => aggressive cancer
pyruvate
Cancers tend to have
- selective expression of PKM2 (instead of PKM1), causing return to FETAL phenotype.
[step: phosphoenolpyruvate -->pyruvate]
- inactivation of PDC (pyruvate dehydrogenase complex): basis for the controversial canadian DCA cancer therapy in that DCA inhibits PDH kinase by irreversible binding to the pyruvate site, which results in the re-activation of PDC, and eventual restoration of aerobic respiration, proper mitochondrial function hence apoptosis.
[step: pyruvate --> acetyl CoA]
- high expression of transcription factor HIF (hypoxia inducible factor): the expression of enzymes for both above steps, and many other key players, such as Glut-1 (gluocose transporter), VEGF and some MMPs/cathepsin, are regulated by HIF. I am sure you are familiar with avastin
glucose surge => enhanced tumor anaerobic metabolism => hypoxia => HIF => expression of cancer growth, angiogenesis, metastasis related proteins => aggressive cancer
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