論文 - 詳細
| RRC ID | 47460 |
|---|---|
| 著者 | Chanmee T, Ontong P, Izumikawa T, Higashide M, Mochizuki N, Chokchaitaweesuk C, Khansai M, Nakajima K, Kakizaki I, Kongtawelert P, Taniguchi N, Itano N. |
| タイトル | Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling. |
| ジャーナル | J Biol Chem |
| Abstract |
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-1α accumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α 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. |
| 巻・号 | 291(46) |
| ページ | 24105-24120 |
| 公開日 | 2016-11-11 |
| DOI | 10.1074/jbc.M116.751263 |
| PII | S0021-9258(20)34680-9 |
| PMID | 27758869 |
| PMC | PMC5104936 |
| MeSH | Animals Female Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) Hexosamines / biosynthesis* Hexosamines / genetics Hyaluronic Acid / biosynthesis* Hyaluronic Acid / genetics Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Mammary Neoplasms, Experimental / genetics Mammary Neoplasms, Experimental / metabolism* Mammary Neoplasms, Experimental / pathology Mice Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / pathology Nitrogenous Group Transferases / genetics Nitrogenous Group Transferases / metabolism Signal Transduction* |
| IF | 4.238 |
| 引用数 | 29 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | AxCANCre (RDB01748) |