CTNNB1, encoding β-catenin, is frequently mutated in hepatocellular carcinoma, the most rapidly growing solid cancer in the US, and activating mutations in this gene are associated with increased expression of glutamine synthetase.A new report by Adebayo Michael et al.
This finding provides better understanding of TRAP1-mediated glutamine metabolism through GS activity, and evidence that TRAP1 could be a promising therapeutic target for glutamine-addicted cancer.
When referred to stromal cells, GS expression might acquire a 'bad' significance to the point that GS inhibition might be considered a conceivable strategy against cancer metastasis.
These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.
Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90.