Journal
NATURE COMMUNICATIONS
Volume 3, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms1786
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Funding
- Japan Society for the Promotion of Science (JSPS), Japan [LS071]
- National Institute of Biomedical Innovation (NIBIO), Japan [09-25]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [21791184, 22791190]
- Sagawa Foundation for the Promotion of Cancer Research
- International Science & Technology Cooperation Project of China and Japan [2010DFA31900]
- Cancer Research UK [11563] Funding Source: researchfish
- Medical Research Council [MC_PC_12004] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [22390298, 21791184, 22791190, 24659695] Funding Source: KAKEN
- MRC [MC_PC_12004] Funding Source: UKRI
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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.
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