Cyp2s1-KO Mouse

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, likely via the Aryl Hydrocarbon Receptor (AHR) pathway, and expressed in epithelial cells of various extrahepatic tissues like the respiratory, gastrointestinal, and urinary tracts, and skin. It may metabolize toxic, carcinogenic, and endogenous compounds such as retinoic acid, and is involved in cell proliferation, lipid metabolism, and potentially immune response regulation [2,6].

In BRAFV600E-driven thyroid cancers, CYP2S1 is highly expressed and acts as a synthetic lethal partner of BRAFV600E. Knockdown of CYP2S1 selectively inhibits the proliferation, migration, invasion, and tumorigenic potential of BRAFV600E-mutated thyroid cancer cells [1]. In psoriasis, CYP2S1 might inhibit keratinocyte proliferation and modulate immune response through regulating cytokines like IL-8, IL-33, and IL-36 [3]. In breast cancer, low cytoplasmic CYP2S1 expression is associated with adverse breast-cancer-specific survival [4]. In lung cancer, knockdown of CYP2S1 inhibits cell proliferation, invasion, migration in vitro and tumor growth in vivo, and high CYP2S1 expression is an unfavorable prognostic marker [5]. In colorectal cancer, CYP2S1 knockdown promotes cell proliferation through increasing prostaglandin E2 (PGE2) levels, which activates β-catenin signaling [7].

In summary, CYP2S1 plays crucial roles in multiple disease-related biological processes including cell proliferation, migration, invasion, and immune response. Model-based research, such as knockdown experiments in relevant cell lines and xenograft mouse models, has revealed its significance in diseases like thyroid, breast, lung, and colorectal cancers, as well as psoriasis. These findings contribute to understanding disease mechanisms and may offer potential therapeutic targets.

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. Sheng, Yujun, Wen, Leilei, Zheng, Xiaodong, Tang, Lili, Zhou, Fusheng. 2020. CYP2S1 might regulate proliferation and immune response of keratinocyte in psoriasis. In Epigenetics, 16, 618-628. doi:10.1080/15592294.2020.1814486. https://pubmed.ncbi.nlm.nih.gov/32924783/

4. Aiyappa-Maudsley, Radhika, Storr, Sarah J, Rakha, Emad A, Ellis, Ian O, Martin, Stewart G. 2022. CYP2S1 and CYP2W1 expression is associated with patient survival in breast cancer. In The journal of pathology. Clinical research, 8, 550-566. doi:10.1002/cjp2.291. https://pubmed.ncbi.nlm.nih.gov/35902379/

5. 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/

6. Yan, Pan, Eng, Ong Chin, Yu, Chieng Jin. . A Review on the Expression and Metabolic Features of Orphan Human Cytochrome P450 2S1 (CYP2S1). In Current drug metabolism, 19, 917-929. doi:10.2174/1389200219666180528090237. https://pubmed.ncbi.nlm.nih.gov/29804525/

7. 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/