Fig. 2

Signalling pathways of IR-induced EMT, metastasis, CSCs, and oncogenic metabolism. Ionizing radiation (IR) causes DNA damage directly, by ionization, or indirectly, by the production of reactive oxygen species (ROS) in tumours. In response to DNA damage, p53 is activated and it exerts the therapeutic effects of IR: induction of cell cycle arrest, apoptosis, autophagy, or senescence. However, IR is also known to enhance the metastatic potential of cancer cells by inducing EMT. IR-induced EMT is mediated by transcription factors (including Snail, HIF-1, ZEB1, Twist, and STAT3) that are activated by signalling pathways (including those of TGF-β, Wnt, Hedgehog, Notch, G-CSF, EGFR/PI3K/Akt, CXCL12/CXCR4, PAI-1, and MAPK). ROS are implicated in IR-induced EMT via the activation of these transcription factors and signalling pathways. Cancer cells that undergo EMT also acquire stemness and oncogenic metabolisms. In addition, EMT, CSCs, and oncogenic metabolism are known to contribute to the radioresistance of cancer cells