Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels.
Harada H., Inoue M., Itasaka S., Hirota K., Morinibu A., Shinomiya K., Zeng L., Ou G., Zhu Y., Yoshimura M., McKenna WG., Muschel RJ., Hiraoka M.
Tumour recurrence frequently occurs after radiotherapy, but the characteristics, intratumoural localization and post-irradiation behaviour of radioresistant cancer cells remain largely unknown. Here we develop a sophisticated strategy to track the post-irradiation fate of the cells, which exist in perinecrotic regions at the time of radiation. Although the perinecrotic tumour cells are originally hypoxia-inducible factor 1 (HIF-1)-negative, they acquire HIF-1 activity after surviving radiation, which triggers their translocation towards tumour blood vessels. HIF-1 inhibitors suppress the translocation and decrease the incidence of post-irradiation tumour recurrence. For the first time, our data unveil the HIF-1-dependent cellular dynamics during post-irradiation tumour recurrence and provide a rational basis for targeting HIF-1 after radiation therapy.