Control of glioma cell death and differentiation by PKM2-Oct4 interaction.

Abstract:

:Glioma stem cells are highly resistant to cell death and as such are supposed to contribute to tumor recurrence by eluding anticancer treatments. Here, we show that spheroids that contain rat neural stem cells (NSCs) or rat glioma stem cells (cancer stem cells, CSCs) express isoforms 1 and 2 of pyruvate kinase (PKM1 and PKM2); however, the expression of PKM2 is considerably higher in glioma spheroids. Silencing of PKM2 enhances both apoptosis and differentiation of rat and human glioma spheroids. We establish that PKM2 was implicated in glioma spheroid differentiation through its interaction with Oct4, a major regulator of self-renewal and differentiation in stem cells. The small molecule Dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, increases the amount of PKM2/Oct4 complexes and thus inhibited Oct4-dependent gene expression. Taken together, our results highlight a new molecular pathway through which PKM2 can manage gliomagenesis via the control of glioma stemness by Oct4.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Morfouace M,Lalier L,Oliver L,Cheray M,Pecqueur C,Cartron PF,Vallette FM

doi

10.1038/cddis.2013.561

subject

Has Abstract

pub_date

2014-01-30 00:00:00

pages

e1036

issn

2041-4889

pii

cddis2013561

journal_volume

5

pub_type

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