Slc7a2, a cationic amino acid transporter, plays a crucial role in various biological processes. It is involved in the transport of amino acids such as lysine and arginine, and is associated with pathways related to amino acid metabolism, histone modification, and immune response. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its functions [1,3,6,7].

In cancer, loss of Slc7a2 has different effects. In hepatocellular carcinoma, SLC7A2 deficiency promotes cancer progression by enhancing recruitment of myeloid-derived suppressor cells via the PI3K/Akt/NF-κB-CXCL1 pathway [3]. In non-small-cell lung cancer, lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis [4]. In ovarian cancer, knockdown of SLC7A2 promotes cell viability, invasion and migration [5]. In triple negative breast cancer, SLC7A2 is downregulated, and its low levels are associated with advanced stages and lymph node metastasis [2]. In glioblastoma stem cells, upregulation of SLC7A2 reprograms lysine catabolism, affecting histone crotonylation and tumour immunity [1]. In pancreatic islet α cells, Slc7a2 knockout in mice leads to decreased arginine-stimulated glucagon and insulin secretion, indicating its role in α cell function and proliferation [6]. Also, interruption of glucagon signaling-induced islet non-alpha cell proliferation is SLC7A2-dependent [7].

In summary, Slc7a2 is essential for amino acid-related functions in normal cells like pancreatic islet cells. In cancer, its dysregulation is associated with tumour progression, metastasis, drug resistance and immune evasion, as revealed by KO/CKO mouse models and other loss-of-function experiments. Understanding Slc7a2 may offer new therapeutic strategies for cancer and insights into pancreatic islet-related functions.

References:

1. Yuan, Huairui, Wu, Xujia, Wu, Qiulian, Snyder, Nathaniel W, Rich, Jeremy N. 2023. Lysine catabolism reprograms tumour immunity through histone crotonylation. In Nature, 617, 818-826. doi:10.1038/s41586-023-06061-0. https://pubmed.ncbi.nlm.nih.gov/37198486/

2. Sun, Yuanyuan, Li, Yaqing, Jiang, Chengying, Liu, Chenying, Song, Yuanming. . SLC7A2-Mediated Lysine Catabolism Inhibits Immunosuppression in Triple Negative Breast Cancer. In Critical reviews in eukaryotic gene expression, 34, 31-43. doi:10.1615/CritRevEukaryotGeneExpr.2024052503. https://pubmed.ncbi.nlm.nih.gov/38842202/

3. Xia, Suhong, Wu, Jingwen, Zhou, Wangdong, Tian, Dean, Liao, Jiazhi. 2021. SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells. In Cell death & disease, 12, 570. doi:10.1038/s41419-021-03853-y. https://pubmed.ncbi.nlm.nih.gov/34108444/

4. Jiang, Shanshan, Zou, Junrong, Dong, Jianyu, Duan, Xianglong, Li, Wensheng. 2023. Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC. In Cell communication and signaling : CCS, 21, 9. doi:10.1186/s12964-022-01023-x. https://pubmed.ncbi.nlm.nih.gov/36639771/

5. Sun, Tianshui, Bi, Fangfang, Liu, Zhuonan, Yang, Qing. 2020. SLC7A2 serves as a potential biomarker and therapeutic target for ovarian cancer. In Aging, 12, 13281-13296. doi:10.18632/aging.103433. https://pubmed.ncbi.nlm.nih.gov/32647070/

6. Spears, Erick, Stanley, Jade E, Shou, Matthew, Powers, Alvin C, Dean, E Danielle. 2023. Pancreatic islet α cell function and proliferation requires the arginine transporter SLC7A2. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.10.552656. https://pubmed.ncbi.nlm.nih.gov/37645716/

7. Coate, Katie C, Dai, Chunhua, Singh, Ajay, Chen, Wenbiao, Dean, E Danielle. 2024. Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners. In Molecular metabolism, 90, 102050. doi:10.1016/j.molmet.2024.102050. https://pubmed.ncbi.nlm.nih.gov/39433176/