Box 8.

Signal Transducer and Activator of Transcription 3 (STAT3).

STAT3 is a transcription factor and transcription activator and its activity is induced by members of the interleukin-6 (IL-6) cytokine family via phosphorylation by Janus family kinases (JAKs) that enables translocation of STAT3 into the cell nucleus.137,142 STAT3 knock out is lethal in embryos, but in adult tissues, conditional knock out results in mild phenotypes and has multiple, sometimes seemingly contradictory, functions. 142 For example, STAT3 has been found to be involved in self-renewal of stem cells and in differentiation of (cancer) stem cells into progenitor cells, or in upregulation of OXPHOS and downregulation of ROS production. STAT3 can also be translocated into mitochondria to promote OXPHOS by binding to complex 1 and it also induces expression of OXPHOS-related genes. 137 Regulatory T cells (Tregs) in GSC niches produce IL-6 and promote GSC stemness via IL-6-STAT3 signaling. 143 Effects of inhibition of STAT3 on stemness of GSCs are presently being investigated.144–147

Abbreviations: OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species; GSCs, glioblastoma stem cells.