Figure 7.

Schematic representation of the role of DCA in PKM2:Oct4-controlled glioma spheroids' differentiation and death. PKM2 activity is controlled by its substrate and oscillates between a dimeric (low activity) form and a tetrameric (high activity) form. The tetrameric form of PKM2 that produces pyruvate from phosphoenolpyruvate (PEP) is the main form in normal differentiated tissues and proliferating cells. In tumor cells, PKM2 is mainly dimeric and dimers are induced by the interaction with several oncogenes. Here, we show that Dichloroacetate induce both the tetrameric form and the interaction with Oct4. This interaction is responsible for the decrease in the transcription activity of Oct4 and thus induces the differentiation of glioma spheroids. The latter process is accompanied by an increase in the sensitivity of CSC to apoptosis. We have previously shown that DCA also sensibilizes glioma spheroids to apoptosis by modifying the expression of members of the Bcl-2 family and via the induction of p53 and FoxO3a activities (Morfouace et al.²¹). In addition to PKM2–Oct4 interaction, both FoxO3a and p53 can have additional roles in the differentiation of glioma spheroids