Reference - Detail
| RRC ID | 6832 |
|---|---|
| Author | Liu X, Wang X, Zhang J, Lam EK, Shin VY, Cheng AS, Yu J, Chan FK, Sung JJ, Jin HC. |
| Title | Warburg effect revisited: an epigenetic link between glycolysis and gastric carcinogenesis. |
| Journal | 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. |
| Volume | 29(3) |
| Pages | 442-50 |
| Published | 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 |
| Times Cited | 124 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY GENETICS & HEREDITY ONCOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Kato III(RCB2088) MKN28(RCB1000) MKN45(RCB1001) |