SOX transcription factors and glioma stem cells: Choosing between stemness and differentiation

Figure 8 Schematic illustration of the involvement of SOX2 and SOX9 in the chemoresistance and radioresistance of glioma stem cells. The expression of stemness-related transcription factor SOX2 is elevated in glioma stem cells (GSCs) through various mechanisms (decreased expression of miR-145 and miR-9* that directly target SOX2, direct transcriptional activation by Forkhead box M1 and through mammalian target of rapamycin signaling) contributing to chemo- and radioresistance of GSCs. SOX2 directly activates the expression of ABCC3 and ABCC6 transporters. mTOR signaling affects the SOX2/SOX9 axis, contributing to chemoresistance. The ERK1/2/miR-124/SOX9 axis and direct targeting of PDK1 (pyruvate dehydrogenase kinase 1) by SOX9 have a role in resistance to radiation and temozolomide, respectively. References are included in the main text. GSCs: Glioma stem cells; FOXM1: Forkhead box M1; mTOR: Mammalian target of rapamycin; PDK1: Pyruvate dehydrogenase kinase 1.