Slc17a9-flox Mouse

Slc17a9, also known as VNUT (vesicular nucleotide transporter), is a transmembrane protein encoding a vesicular ATP transport protein. It functions in lysosomes and other secretory vesicles, playing a crucial role in maintaining lysosomal function and cell viability, and is involved in multiple biological processes. It has been associated with pathways like the PI3K/Akt signaling pathway [3].

In cancer research, Slc17a9 has shown significant implications. In clear cell renal cell carcinoma (ccRCC), its knockdown inhibited cancer cell proliferation, migration, and invasion, while overexpression promoted a more malignant phenotype both in vitro and in vivo. It was found to upregulate PTHLH, promoting epithelial-mesenchymal transition (EMT) in ccRCC [1]. In hepatocellular carcinoma (HCC), the HHEX-ABI2/Slc17a9 axis was shown to induce cancer stem cell-like properties and tumorigenesis [2]. Additionally, in non-small cell lung cancer (NSCLC), its up-regulation was correlated with survival, and knockdown significantly inhibited cell proliferation and ATP levels in lung cancer cells [5]. In gastric, colorectal cancers, high Slc17a9 expression was associated with poor survival, suggesting it could be a prognostic biomarker [4,8]. In osteoblasts, knockdown of Slc17a9 reduced extracellular ATP levels and led to increased osteoblast differentiation in response to compressive force [6]. In the context of heart-brain interaction during pressure overload, adrenergic neuron-specific knockout of Slc17a9 reduced cardiac extracellular ATP level, inhibited NLRP3 inflammasome activation, IL-1β production, and adaptive cardiac hypertrophy [7].

In conclusion, Slc17a9 is essential for maintaining cell viability through regulating lysosomal function. Its role in multiple cancer types, osteoblast differentiation, and cardiac inflammation and hypertrophy has been revealed through various gene-knockout and knockdown experiments. These findings suggest that Slc17a9 could be a potential therapeutic target and prognostic biomarker in related diseases.