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The gene encoding β-catenin is frequently mutated in hepatocellular carcinoma cells. While the oncogenicity of β-catenin has been extensively studied, β-catenin's role in hepatocellular carcinoma tumor metabolism is currently less well understood. In this study, we found that β-catenin regulates the expression of glutamine synthetase and triggers a series of metabolic changes leading to induction of autophagy in hepatocellular carcinoma cells. β-Catenin-active Hep3B and HepG2 cells exhibited higher basal levels of autophagic activity than did β-catenin wild-type cells. We also found that autophagy in β-catenin-active cells was mediated by glutamine synthetase, as silencing of glutamine synthetase significantly reduced autophagic activity. We also showed that β-catenin-active hepatocellular carcinoma cells were more sensitive to sorafenib than were β-catenin wild-type cells. Our results demonstrated that glutamine synthetase-mediated autophagy explains the high sensitivity of β-catenin-active hepatocellular carcinoma cells to sorafenib. Our results highlight the importance of glutamine metabolism in the regulation of autophagy in hepatocellular carcinoma cells. More importantly, our study unravels the molecular mechanisms leading to sorafenib sensitivity in hepatocellular carcinoma.
This article was published in the following journal.
Name: Experimental & molecular medicine
Kinase inhibitor sorafenib is the most widely used drug for advanced HCC clinical treatment nowadays. However, sorafenib administration is only effective for a small portion of HCC patients, and the m...
Although sorafenib enhances overall survival, sorafenib resistance has been reported to be a significant limiting factor for improved prognosis in patients with hepatocellular carcinoma (HCC). Therefo...
Hepatocellular carcinoma (HCC) is a highly invasive cancer associated with high mortality rates. Although sorafenib is currently recommended as standard treatment for advanced HCC, its treatment effic...
Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only FDA approved first-line targeted drug for advanced HCC, but its effect on patients'...
To evaluate the cost-effectiveness of sorafenib treatment in combination with other therapies versus sorafenib monotherapy among patients with advanced hepatocellular carcinoma (HCC) who are enrolled ...
This is a Phase I study, which means that the goal is to see if the combination of Temsirolimus and Sorafenib is safe in patients with Hepatocellular Carcinoma. Sorafenib is a standard tre...
The PI is studying if sorafenib/hydroxychloroquine (HCQ) will have improved efficacy when compared to sorafenib alone and in patients progressing of sorafenib the addition of HCQ would lea...
The purpose of the study is to determine whether 4SC-201 alone or in combination with Sorafenib is effective and safe in the treatment of hepatocellular carcinoma in patients refractory to...
60 patients of radiological, biopsy proven advanced HCC (Hepatocellular carcinoma) patient will be randomized into two groups. Cases group will receive Sorafenib plus vitamin K and control...
This Phase I study of sorafenib in high risk hepatocellular cancer patients after liver transplantation will study 24 subjects for about 5 years. Each subject will receive sorafenib for 6 ...
A multi-functional catenin that is highly homologous to BETA CATENIN. Gamma catenin binds CADHERINS and helps link their cytoplasmic tails to ACTIN in the CYTOSKELETON via ALPHA CATENIN. It is also found in DESMOSOMES where it mediates the link between DESMOSOMAL CADHERINS and DESMOPLAKIN.
A catenin that binds F-ACTIN and links the CYTOSKELETON with BETA CATENIN and GAMMA CATENIN.
A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.
A specific complex of WNT SIGNALING PATHWAY proteins that mediates the phosphorylation-dependent destruction of cytosolic BETA-CATENIN. The complex is disrupted by cell surface binding of WNT PROTEINS, which allows beta-catenin levels to rise to the point where they migrate to the CELL NUCLEUS and activate transcription.
Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...