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. 2016 Dec 22;8(4):6376–6398. doi: 10.18632/oncotarget.14093

Figure 10. Putative scheme depicting changes in iron metabolism of tumor-initiating cells (TICs).

Figure 10

TICs show higher levels of labile iron pool (LIP) and subsequently higher reactive oxygen species (ROS) which in connection with lower Fes cluster biogenesis (lower expression of ABCB10 and GLRX5) leading to accumulation of iron in mitochondria and possibly affecting genome stability and increasing plasticity of these cells. Alterations in the FeS cluster assembly lead to reduced activity of ACO1/IRP1 as well as mitochondrial respiratory complex I. The IRP binding activity of ACO1 is elevated resulting in higher TFRC and lower ferritin levels. Furthermore, TICs show an increase in the protein level of of EPAS1/ HIF2A connected with higher iron uptake (CYBRD1, TFRC) as well as with the extracellular matrix remodelling and redox balance equilibrium via the expression of QSOX1. On the other hand, reduced glutathione (GSH) is lower in TICs and these cells seem to be in a more pro-oxidative state and contain lower protein levels of IREB2/IRP2 likely reflecting increased LIP.