title: Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels.
abstract: 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.
authors.affiliation: Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Sakyo-ku 606-8501, Japan. hharada@kuhp.kyoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itasaka
authors.forename: Kiichi
authors.initials: K
authors.lastname: Hirota
authors.forename: Akiyo
authors.initials: A
authors.lastname: Morinibu
authors.forename: Kazumi
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Lihua
authors.initials: L
authors.lastname: Zeng
authors.forename: Guangfei
authors.initials: G
authors.lastname: Ou
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Michio
authors.initials: M
authors.lastname: Yoshimura
authors.forename: W Gillies
authors.initials: WG
authors.lastname: McKenna
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Muschel
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000528:radiation effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology* / Q000532:radiotherapy*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D051793:Hypoxia-Inducible Factor 1