Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels

被引：170

作者：

Harada, Hiroshi ^{[1
,2
]}

Inoue, Masahiro ^{[3
]}

Itasaka, Satoshi ^{[2
]}

Hirota, Kiichi ^{[4
]}

Morinibu, Akiyo ^{[1
]}

Shinomiya, Kazumi ^{[1
]}

Zeng, Lihua ^{[1
,2
,5
]}

Ou, Guangfei ^{[2
]}

Zhu, Yuxi ^{[1
,2
]}

Yoshimura, Michio ^{[2
,6
]}

McKenna, W. Gillies ^{[6
]}

Muschel, Ruth J. ^{[6
]}

Hiraoka, Masahiro ^{[2
]}

机构：

[1] Kyoto Univ, Grp Radiat & Tumor Biol, Career Path Promot Unit Young Life Scientists, Sakyo Ku, Kyoto 6068501, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Radiat Oncol & Image Appl Therapy, Sakyo Ku, Kyoto 6068507, Japan

[3] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Biochem, Higashinari Ku, Osaka 5378511, Japan

[4] Kyoto Univ, Dept Anesthesia, Kyoto Univ Hosp, Sakyo Ku, Kyoto 6068507, Japan

[5] Fourth Mil Med Univ, Dept Radiat Med, Xian 710032, Shaanxi, Peoples R China

[6] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

基金：

日本学术振兴会;

关键词：

HYPOXIA-INDUCIBLE FACTOR-1; FACTOR-I; INTERMITTENT HYPOXIA; RECOMBINASE ACTIVITY; MAMMALIAN-CELLS; CRE RECOMBINASE; FREE-RADICALS; EXPRESSION; OXYGEN; RADIOSENSITIVITY;

D O I：

10.1038/ncomms1786

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：10

共 52 条

[1]

Hypoxia-inducible factor-1α (HIF-1α) escapes O2-driven proteasomal degradation irrespective of its subcellular localization:: nucleus or cytoplasm [J].