CYP2S1, a member of the cytochrome P450 superfamily, is located on chromosome 19q13.2 within a cluster with other CYP2 family members. It is inducible by dioxin via the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT), and is expressed in epithelial cells of many extrahepatic tissues, such as the respiratory, gastrointestinal, and urinary tracts, and the skin. It is likely involved in metabolizing toxic and carcinogenic compounds, as well as important endogenous substrates like retinoic acid [2].

In BRAFV600E-driven thyroid cancers, CYP2S1 was identified as a synthetic lethal partner of BRAFV600E. Knockdown of CYP2S1 selectively inhibited cell proliferation, migration, invasion and tumorigenic potential in nude mice, and promoted apoptosis in BRAFV600E-mutated thyroid cancer cells [1]. In lung cancer, knockdown of CYP2S1 decreased cell proliferation, invasion, and migration in vitro and inhibited lung cancer cell growth in vivo. GSEA analysis suggested it functions by regulating E2F targets and G2M checkpoint pathway involved in the cell cycle [3]. In colorectal cancer, CYP2S1 knockdown promoted cell proliferation through increasing the level of endogenous prostaglandin E2 (PGE2), which activated β-catenin signaling, and also increased tumor growth in a xenograft mouse model [4].

In conclusion, CYP2S1 is an important gene involved in multiple biological processes and disease conditions. Studies using knockdown or knockout models in various cancers, such as thyroid, lung, and colorectal cancers, have revealed its role in regulating cell proliferation, migration, invasion, and apoptosis. These findings provide valuable insights into the mechanisms of these diseases and suggest CYP2S1 could be a potential therapeutic target.

References:

1. Li, Yiqi, Su, Xi, Feng, Chao, Ji, Meiju, Hou, Peng. 2020. CYP2S1 is a synthetic lethal target in BRAFV600E-driven thyroid cancers. In Signal transduction and targeted therapy, 5, 191. doi:10.1038/s41392-020-00231-6. https://pubmed.ncbi.nlm.nih.gov/32913191/

2. Saarikoski, Sirkku T, Rivera, Steven P, Hankinson, Oliver, Husgafvel-Pursiainen, Kirsti. . CYP2S1: a short review. In Toxicology and applied pharmacology, 207, 62-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16054184/

3. Guo, Huan, Zeng, Baozhen, Wang, Liqiong, Song, Xin, Zhang, Peixian. . Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration. In Cancer biomarkers : section A of Disease markers, 32, 531-539. doi:10.3233/CBM-210189. https://pubmed.ncbi.nlm.nih.gov/34275895/

4. Yang, Chao, Li, Changyuan, Li, Minle, He, Lin, Wan, Chunling. 2014. CYP2S1 depletion enhances colorectal cell proliferation is associated with PGE2-mediated activation of β-catenin signaling. In Experimental cell research, 331, 377-86. doi:10.1016/j.yexcr.2014.12.008. https://pubmed.ncbi.nlm.nih.gov/25557876/