Agami Lab

Netherlands Cancer Institute

West-Nederland (NL3) · Netherlands

ERC-funded
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ERC Advanced Grant · 2023

Causes and consequences of aberrant mRNA translation in cancer

Shortages in amino acids are weapons in the warfare between tumor cells and tumor-infiltrating lymphocytes. Tumor cells enhance or inhibit the production of key amino acid metabolites to stimulate oncogenesis and suppress anti-tumor activity. A key player in this battle is tryptophan. Activated T cells secrete interferon-γ, which upregulates IDO1 enzyme to catabolize tryptophan to kynurenine in target tumor cells. While kynurenine suppresses T-cell function, its production limits tryptophan availability in tumor cells. Importantly, as tumor cells almost invariably deregulate mRNA translation to promote proliferation and metastasis, the consequences of tryptophan shortage are major. It…

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