Slc17a9, also known as VNUT (vesicular nucleotide transporter), functions as an ATP transporter in lysosomes and other secretory vesicles [5]. It is involved in multiple biological processes, such as regulating osteoblast differentiation [8], and may participate in pathways like the PI3K/Akt signaling pathway [7]. Dysregulation of Slc17a9 has been linked to various diseases, highlighting its biological importance.

In cancer research, knockdown of Slc17a9 in renal cancer cells inhibited their proliferation, migration, and invasion, while overexpression led to a more malignant phenotype both in vitro and in vivo, suggesting its role in promoting the progression of clear cell renal cell carcinoma through the SLC17A9-PTHLH-EMT axis [1]. In hepatocellular carcinoma, HHEX-mediated ABI2 upregulated Slc17a9 to promote cancer stem cell-like properties and tumorigenesis [2]. In gastric carcinoma, high Slc17a9 expression was associated with poor overall and recurrence-free survival [3]. In non-small cell lung cancer, Slc17a9 up-regulation was correlated with overall survival, and its knockdown inhibited cell proliferation and ATP levels [4]. In hepatocellular carcinoma, high Slc17a9 expression was related to poor prognosis [6,7]. In colorectal cancer, Slc17a9 overexpression was associated with advanced tumor stages and poor survival, and it was an independent prognostic predictor [9].

In conclusion, Slc17a9 plays a crucial role in regulating cell viability, as well as in the development and progression of multiple cancers. Studies on Slc17a9, especially through loss-of-function experiments in cell lines, have provided valuable insights into its functions in disease processes, potentially offering new targets for cancer diagnosis and treatment.

References:

1. Li, Weiquan, Xu, Ning, Meng, Xiangui, Xiao, Wen, Zhang, Xiaoping. 2022. SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma. In iScience, 26, 105764. doi:10.1016/j.isci.2022.105764. https://pubmed.ncbi.nlm.nih.gov/36590170/

2. Li, Huizi, Liu, Jin, Lai, Jie, Zhang, Tong, Gu, Qiuping. 2024. The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC. In Journal of translational medicine, 22, 537. doi:10.1186/s12967-024-05324-2. https://pubmed.ncbi.nlm.nih.gov/38844969/

3. Li, Junqing, Su, Taiqiang, Yang, Liang, Zhang, Changhua, He, Yulong. 2019. High SLC17A9 expression correlates with poor survival in gastric carcinoma. In Future oncology (London, England), 15, 4155-4166. doi:10.2217/fon-2019-0283. https://pubmed.ncbi.nlm.nih.gov/31799885/

4. Gao, Yan, Chen, Yijia, Liu, Min, Ke, Changbin, Pei, Zhijun. 2023. SLC17A9 as a prognostic biomarker correlated with immune infiltrates in human non-small cell lung cancer. In American journal of cancer research, 13, 3963-3982. doi:. https://pubmed.ncbi.nlm.nih.gov/37818081/

5. Huang, Peng, Cao, Qi, Xu, Mengnan, Dong, Xian-Ping. 2022. Lysosomal ATP Transporter SLC17A9 Controls Cell Viability via Regulating Cathepsin D. In Cells, 11, . doi:10.3390/cells11050887. https://pubmed.ncbi.nlm.nih.gov/35269509/

6. Wu, Jingdong, Yang, Yongfei, Song, Jiansheng. 2020. Expression of SLC17A9 in hepatocellular carcinoma and its clinical significance. In Oncology letters, 20, 182. doi:10.3892/ol.2020.12043. https://pubmed.ncbi.nlm.nih.gov/32934749/

7. Kui, Xue-Yan, Gao, Yan, Liu, Xu-Sheng, Zhang, Yao-Hua, Pei, Zhi-Jun. 2022. Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma. In Frontiers in oncology, 12, 809847. doi:10.3389/fonc.2022.809847. https://pubmed.ncbi.nlm.nih.gov/35957868/

8. Inoue, Asako, Nakao-Kuroishi, Kayoko, Kometani-Gunjigake, Kaori, Kokabu, Shoichiro, Kawamoto, Tatsuo. 2020. VNUT/SLC17A9, a vesicular nucleotide transporter, regulates osteoblast differentiation. In FEBS open bio, 10, 1612-1623. doi:10.1002/2211-5463.12918. https://pubmed.ncbi.nlm.nih.gov/32592329/

9. Yang, Liang, Chen, Zhihui, Xiong, Weixin, Song, Xinming, Liu, Jia. 2018. High expression of SLC17A9 correlates with poor prognosis in colorectal cancer. In Human pathology, 84, 62-70. doi:10.1016/j.humpath.2018.09.002. https://pubmed.ncbi.nlm.nih.gov/30236596/