Iron Metabolism in Cancer and Senescence: A Cellular Perspective

Simple Summary Iron is an essential element in human cells. Cells use iron for many processes, such as proliferation, survival, DNA synthesis and energy production. However, iron overload is dangerous and can cause damage to cells. Hence, iron metabolism and balance are tightly regulated in order to avoid iron accumulation or iron depletion. Studies published in recent years have demonstrated that iron metabolism is dysregulated in cancer cells and that such alterations help the tumor to grow, invade and survive anticancer therapies. For these reasons, iron represents a potential useful target for cancer therapy. The dysregulation of iron metabolism has also been observed in senescent cells, but in this case, our knowledge is still expanding. In this review, we first provide an overview of iron metabolism and iron regulatory proteins. Then, we summarize what we currently know about iron balance in cancer cells and senescent cells. Iron participates in a number of biological processes and plays a crucial role in cellular homeostasis. Alterations in iron metabolism are considered hallmarks of cancer and drivers of aggressive behaviors, such as uncontrolled proliferation, resistance to apoptosis, enhanced metastatic ability, increased cell plasticity and stemness. Furthermore, a dysregulated iron metabolism has been associated with the development of an adverse tumor microenvironment. Alterations in iron metabolism have been described in cellular senescence and in aging. For instance, iron has been shown to accumulate in aged tissues and in age-related diseases. Furthermore, in vitro studies demonstrate increases in iron content in both replicative and stress-induced senescent cells. However, the role, the mechanisms of regulation and dysregulation and the effects of iron metabolism on senescence remain significantly less characterized. In this review, we first provide an overview of iron metabolism and iron regulatory proteins. Then, we summarize alterations in iron homeostasis in cancer and senescence from a cellular point of view.