Metabolic consequences of TKTL1 suppression
Suppression of TKTL1 by shRNA constructs, leads to a lower glucose consumption rate and an about 30% less lactate production rate, suggesting that TKTL1 plays a major role in lactate production via the PPP. Furthermore suppression of TKTL1 leads to regaining of mitochondrial function, a reduction of HIF-1 alpha and a reduction of phosphorylated Akt.
TKTL1 suppressed cells have an increased intracellular ROS concentration, have a decreased anti ROS defence and are more susceptible to oxidative stress induced apoptosis which leads to enhanced sensitivity to chemo and radiation therapy.
Cancer cells without suppression of TKTL1 grow twice as fast as cancer cells with suppression of TKTL1.