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Glutamine synthetase mediates sorafenib sensitivity in β-catenin-active hepatocellular carcinoma cells.

07:00 EST 5th January 2018 | BioPortfolio

Summary of "Glutamine synthetase mediates sorafenib sensitivity in β-catenin-active hepatocellular carcinoma cells."

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.

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This article was published in the following journal.

Name: Experimental & molecular medicine
ISSN: 2092-6413
Pages: e421

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Medical and Biotech [MESH] Definitions

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.

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