SLC6A19-mediated tryptophan uptake suppresses renal cell carcinoma metastasis via activating NAD⁺-dependent deacetylase SIRT1.

ABSTRACT: Metastasis is the hallmark of lethal renal cell carcinoma (RCC), and the underlying mechanism driving RCC metastasis remains insufficiently understood. Amino acid metabolism remodeling plays a key role in the matastasis of RCC. In this study, we identified SLC6A19, a tryptophan transporter, as a novel suppressor gene of RCC, which is closely correlated with the metastasis and survival of RCC patients. Overexpression of SLC6A19 significantly inhibits RCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, SLC6A19 actively transports tryptophan into cells, facilitating de novo NAD⁺ biosynthesis, which in turn activates the NAD⁺-dependent deacetylase SIRT1. This activation drives the deacetylation of histone H3 at lysine 27 (H3K27), the

SUBMITTER: Chen Z 

PROVIDER: S-EPMC12595055 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature