GEO series

The SLC1A1/EAAT3 Dicarboxylic Amino Acid Transporter is an Epigenetically Dysregulated Nutrient Carrier that Sustains Oncogenic Metabolic Programs

GSE241864 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 8 samples Submitted 2025/01/31 Platform GPL20301

Summary

Inactivation of pVHL tumor suppressor in clear cell Renal Cell Carcinoma (ccRCC) increases the abundance of Histone H3 lysine 27 acetylation (H3K27ac). We hypothesized that H3K27ac, a marker of transcriptional activation, drives the expression of critical oncogenes in ccRCC. Using H3K27ac ChIP-Seq; RNA-Seq; an in vivo positive selection screen; cell-based functional studies; and clinical validations; here, we report the identification of the SLC1A1/EAAT3 aspartate (Asp) and glutamate (Glu) transporter as a ccRCC oncogene. pVHL loss promotes SLC1A1 expression in a HIF-independent manner. SLC1A1 inactivation impedes ccRCC growth both in vitro and in vivo via depletion of Asp/Glu-derived metabolites, and sensitizes ccRCCs to metabolic therapeutics (e.g., glutaminase blockers). In human ccRCC biospecimens, higher SLC1A1 expression is associated with metastatic disease and clusters with elevated expression of other solute careers, but not HIF/Hypoxia pathways. Altogether, our studies identify a HIF-independent metabolic hub in ccRCC and credential SLC1A1 as an actionable ccRCC oncogene.

Published in

The SLC1A1/EAAT3 dicarboxylic amino acid transporter is an epigenetically dysregulated nutrient carrier that sustains oncogenic metabolic programs

Grubb T, Koochaki P, Matar S et al. · Nature communications 2025 · PMID 41238532 · doi:10.1038/s41467-025-64983-x

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Direct links to NCBI, no account and no request form: the whole study as GSE241864_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

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Also filed as BioProject PRJNA1010361 and SRA study SRP457373. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41238532) ↗

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