title: Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance.
abstract: Tumor hypoxia has been attracting increasing attention in the fields of radiation biology and oncology since Thomlinson and Gray detected hypoxic cells in malignant solid tumors and showed that they exert a negative impact on the outcome of radiation therapy. This unfavorable influence has, at least partly, been attributed to cancer cells acquiring a radioresistant phenotype through the activation of the transcription factor, hypoxia-inducible factor 1 (HIF-1). On the other hand, accumulating evidence has recently revealed that, even though HIF-1 is recognized as an important regulator of cellular adaptive responses to hypoxia, it may not become active and induce tumor radioresistance under hypoxic conditions only. The mechanisms by which HIF-1 is activated in cancer cells not only under hypoxic conditions, but also under normoxic conditions, through cancer-specific genetic alterations and the resultant imbalance in intermediate metabolites have been summarized herein. The relevance of the HIF-1-mediated characteristic features of cancer cells, such as the production of antioxidants through reprogramming of the glucose metabolic pathway and cell cycle regulation, for tumor radioresistance has also been reviewed.
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan Hakubi Center, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan hharada@kuhp.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
mesh_terms: D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D011836:Radiation Tolerance
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Warburg effect; cancer; cell cycle; hypoxia-inducible factor 1 (HIF-1); metabolic reprogramming; radioresistance; tumor blood vessels