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2016 ; 6
(ä): 25092
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Discovery of a novel glucose metabolism in cancer: The role of endoplasmic
reticulum beyond glycolysis and pentose phosphate shunt
#MMPMID27121192
Marini C
; Ravera S
; Buschiazzo A
; Bianchi G
; Orengo AM
; Bruno S
; Bottoni G
; Emionite L
; Pastorino F
; Monteverde E
; Garaboldi L
; Martella R
; Salani B
; Maggi D
; Ponzoni M
; Fais F
; Raffaghello L
; Sambuceti G
Sci Rep
2016[Apr]; 6
(ä): 25092
PMID27121192
show ga
Cancer metabolism is characterized by an accelerated glycolytic rate facing
reduced activity of oxidative phosphorylation. This "Warburg effect" represents a
standard to diagnose and monitor tumor aggressiveness with
(18)F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index
of total glucose consumption. Studying cancer metabolic response to respiratory
chain inhibition by metformin, we repeatedly observed a reduction of tracer
uptake facing a marked increase in glucose consumption. This puzzling discordance
brought us to discover that (18)F-fluorodeoxyglucose preferentially accumulates
within endoplasmic reticulum by exploiting the catalytic function of
hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity
decreased both tracer uptake and glucose consumption, caused severe energy
depletion and decreased NADPH content without altering mitochondrial function.
These data document the existence of an unknown glucose metabolism triggered by
hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells.
Besides its basic relevance, this finding can improve clinical cancer diagnosis
and might represent potential target for therapy.