論文 - 詳細
| RRC ID | 6832 |
|---|---|
| 著者 | Liu X, Wang X, Zhang J, Lam EK, Shin VY, Cheng AS, Yu J, Chan FK, Sung JJ, Jin HC. |
| タイトル | Warburg effect revisited: an epigenetic link between glycolysis and gastric carcinogenesis. |
| ジャーナル | Oncogene |
| Abstract |
In cancer cells, glucose is often converted into lactic acid, which is known as the 'Warburg effect'. The reason that cancer cells have a higher rate of aerobic glycolysis, but not oxidative phosphorylation, remains largely unclear. Herein, we proposed an epigenetic mechanism of the Warburg effect. Fructose-1,6-bisphosphatase-1 (FBP1), which functions to antagonize glycolysis was downregulated through NF-kappaB pathway in Ras-transformed NIH3T3 cells. Restoration of FBP1 expression suppressed anchorage-independent growth, indicating the relevance of FBP1 downregulation in carcinogenesis. Indeed, FBP1 was downregulated in gastric carcinomas (P<0.01, n=22) and gastric cancer cell lines (57%, 4/7). Restoration of FBP1 expression reduced growth and glycolysis in gastric cancer cells. Moreover, FBP1 downregulation was reversed by pharmacological demethylation. Its promoter was hypermethylated in gastric cancer cell lines (57%, 4/7) and gastric carcinomas (33%, 33/101). Inhibition of NF-kappaB restored FBP1 expression, partially through demethylation of FBP1 promoter. Notably, Cox regression analysis revealed FBP1 promoter methylation as an independent prognosis predicator for gastric cancer (hazard ratio: 3.60, P=0.010). In summary, we found that NF-kappaB functions downstream of Ras to promote epigenetic downregulation of FBP1. Promoter methylation of FBP1 can be used as a new biomarker for prognosis prediction of gastric cancer. Such an important epigenetic link between glycolysis and carcinogenesis partly explains the Warburg effect. |
| 巻・号 | 29(3) |
| ページ | 442-50 |
| 公開日 | 2010-1-21 |
| DOI | 10.1038/onc.2009.332 |
| PII | onc2009332 |
| PMID | 19881551 |
| MeSH | Aged Animals Cell Line, Tumor Cell Transformation, Neoplastic / genetics Cell Transformation, Neoplastic / metabolism DNA Methylation Down-Regulation Epigenesis, Genetic* Female Fructose-Bisphosphatase / genetics* Fructose-Bisphosphatase / metabolism Glucose / metabolism Glycolysis* Humans Kaplan-Meier Estimate Lactic Acid / metabolism Male Mice Middle Aged NF-kappa B / genetics NF-kappa B / metabolism NIH 3T3 Cells Prognosis Promoter Regions, Genetic / genetics RNA Interference Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / genetics Stomach Neoplasms / metabolism Stomach Neoplasms / pathology* ras Proteins / genetics ras Proteins / metabolism |
| IF | 7.971 |
| 引用数 | 124 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY GENETICS & HEREDITY ONCOLOGY CELL 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 7 |
| 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 | |
| ヒト・動物細胞 | Kato III(RCB2088) MKN28(RCB1000) MKN45(RCB1001) |