Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma, and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of lipid droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect that might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

Automated summary

The study identified that radioresistant cancer cells in breast, bladder, lung, neuroglioma, and prostate showed an increase in lipid droplet (LD) number, with cells containing higher LDs exhibiting greater clonogenic potential after irradiation. The researchers found a close connection between LD content and iron metabolism, particularly with the presence of the ferritin heavy chain (FTH1). Silencing the FTH1 gene in breast and lung cancer cells reduced LD numbers and increased radiosensitivity, while FTH1 overexpression and iron-chelating treatment restored LD levels and radioresistance.