Tumor-initiating cells exhibit profound deregulation of iron metabolism

What is it about?

This article shows that tumor-initiating cells (TICs), also termed cancer stem (-like) cells (CSCs) show marked changes in iron metabolism. These cells exhibit higher intracellular iron labile pool (LIP) and accumulation of iron within mitochondria. They are more susceptible to iron chelation ad show activation of the IRE/IRP system, resulting in higher iron uptake; in other words these cells show dependence on iron and iron withdrawal leads to their death. TICs show, in concordance with high LIP, higher reactive oxygen species (ROS) which probably works in this setting as signaling molecules and through the destabilization of repair enzymes dependent on FeS clusters, it might contribute to higher mutational rate and plasticity of these cells. Importantly, authors also define the deregulated gene signature related to iron metabolism consisting of genes regulating iron uptake, mitochondrial FeS cluster biogenesis and hypoxic response (ABCB10, ACO1, CYBRD1, EPAS1, GLRX5, HEPH, HFE, IREB2, QSOX1 and TFRC).

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Why is it important?

It is one o the first studies defining iron metabolism as a possible target that is altered in tumor-initiating cells/ cancer stem(-like) cells. This study proposes that higher intracellular iron pool, accumulation of iron within mitochondria and higher reactive oxygen species level are linked with the features of cancer stem(-like) cells and targeting them might be a way to either kill them or reprogram them.

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