Fig. 7. Schematic illustration of the mechanism of ANGPTL4 contributing to radioresistance by inhibiting ferroptosis in hypoxic NSCLC.

Solid tumours often contain hypoxic regions and normoxic regions according to the oxygen concentration. Under hypoxia, the expression of ANGPTL4 protein is increased to inhibit cellular ferroptosis, leading to radioresistance of NSCLC. Since ANGPTL4 is a secretory protein, it can be highly contained in the exosomes derived from hypoxic NSCLC. Once the exosomal ANGPTL4 protein is transferred into bystander normoxic tumour cells, it can suppress ferroptosis and thus induce radioresistance of the recipients.