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イタノ ナオキ
ITANO NAOKI
板野 直樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2016/11 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling |
| 執筆形態 | その他 |
| 掲載誌名 | JOURNAL OF BIOLOGICAL CHEMISTRY |
| 出版社・発行元 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 巻・号・頁 | 291(46),pp.24105-24120 |
| 著者・共著者 | Theerawut Chanmee,Pawared Ontong,Tomomi Izumikawa,Miho Higashide,Nobutoshi Mochizuki,Chatchadawalai Chokchaitaweesuk,Manatsanan Khansai,Kazuki Nakajima,Ikuko Kakizaki,Prachya Kongtawelert,Naoyuki Taniguchi,Naoki Itano |
| 概要 | Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), an HBP rate-limiting enzyme, resembled the results of HA overproduction with regard to HIF-1 accumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1 protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling. |
| DOI | 10.1074/jbc.M116.751263 |
| ISSN | 0021-9258/1083-351X |