| RRC ID |
65470
|
| Author |
Yang J, Wang C, Zhao F, Luo X, Qin M, Arunachalam E, Ge Z, Wang N, Deng X, Jin G, Cong W, Qin W.
|
| Title |
Loss of FBP1 facilitates aggressive features of hepatocellular carcinoma cells through the Warburg effect.
|
| Journal |
Carcinogenesis
|
| Abstract |
Reprogrammed metabolism has been identified as an emerging hallmark in cancer cells. It has been demonstrated that fructose-1, 6-bisphosphatase 1 (FBP1) as a rate-limiting enzyme in gluconeogenesis plays critical roles in tumor initiation and progression in several cancer types. However, function of FBP1 in hepatocellular carcinoma (HCC) is still not clear. In this study, we observed that the expression of FBP1 was obviously downregulated in the cell lines and tissues of HCC. Downregulation of FBP1 in HCC tissues was correlated with a lower overall survival rate and had a relatively higher tendency of tumor recurrence (n = 224). Silencing FBP1 could significantly promote colony formation, proliferation and metastasis of HCC cells, while ectopic overexpression of FBP1 resulted in impaired abilities of colony formation, proliferation and metastasis in vitro and in vivo. Mechanistically, silencing FBP1 facilitated glycolysis in HCC cell lines, which may be responsible for aggressiveness of HCC cells. We further found that targeting the Warburg effect using the specific inhibitor FX11 could suppress the aggressiveness of HCC cells which was mediated by loss of FBP1. These findings indicate that FBP1 appears to be a tumor suppressor in HCC. Strategies to restore the levels and activities of FBP1 might be developed to treat patients with HCC.
|
| Volume |
38(2)
|
| Pages |
134-143
|
| Published |
2017-2-1
|
| DOI |
10.1093/carcin/bgw109
|
| PII |
bgw109
|
| PMID |
27742690
|
| MeSH |
Animals
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / pathology
Cell Proliferation / genetics
Cell Transformation, Neoplastic / genetics*
DNA Helicases / antagonists & inhibitors
DNA Helicases / genetics*
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / genetics*
Disease Progression
Gene Expression Regulation, Neoplastic
Gene Silencing
Gluconeogenesis / drug effects
Gluconeogenesis / genetics
Hep G2 Cells
Humans
Liver Neoplasms / drug therapy
Liver Neoplasms / genetics*
Liver Neoplasms / pathology
Mice
Naphthalenes / administration & dosage
Neoplasm Metastasis
RNA-Binding Proteins
Xenograft Model Antitumor Assays
|
| IF |
4.603
|
| Resource |
| Human and Animal Cells |
HuH-7 |
