Fads1-KO Mouse

Fads1, also known as delta-5 desaturase, is a rate-limiting enzyme in long-chain polyunsaturated fatty acid (LCPUFA) synthesis. It catalyzes the conversion of dihomo-gamma-linolenic acid (DGLA) to arachidonic acid (AA), playing a crucial role in fatty acid metabolism. This process is involved in various biological pathways, such as the synthesis of prostaglandin E2 (PGE2) via the TLR4/MYD88 pathway in colorectal cancer cells, and is also relevant to lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer [1,2].

In colorectal cancer, Fads1-arachidonic acid axis promotes tumor growth by altering the intestinal microecology to increase gram-negative bacteria. The elimination of gram-negative microbes abolishes the effect of Fads1 [1]. In triple-negative breast cancer, Fads1/2 high-expressing tumors are susceptible to ferroptosis-inducing agents, and targeting Fads1/2 can render tumors ferroptosis-resistant [2]. In laryngeal squamous cell carcinoma, Fads1 promotes cancer cell proliferation, migration, and invasion by activating the AKT/mTOR signaling pathway [3]. In bladder cancer, high Fads1 expression is associated with advanced clinicopathological features and poor prognosis [4].

In conclusion, Fads1 is essential for fatty acid metabolism and is involved in the development and progression of multiple cancers, including colorectal, triple-negative breast, laryngeal squamous cell, and bladder cancers. The study of Fads1 using in vivo models like gene knockout or conditional knockout mouse models (although not explicitly detailed in all references here) could potentially provide more insights into its role in these disease conditions, helping to understand the underlying mechanisms and potentially develop new therapeutic strategies.

References:

1. Xu, Chunjie, Gu, Lei, Hu, Lipeng, Zhang, Xueli, Xu, Qing. 2023. FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer. In Nature communications, 14, 2042. doi:10.1038/s41467-023-37590-x. https://pubmed.ncbi.nlm.nih.gov/37041160/

2. Lorito, Nicla, Subbiani, Angela, Smiriglia, Alfredo, Bachi, Angela, Morandi, Andrea. 2024. FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer. In EMBO molecular medicine, 16, 1533-1559. doi:10.1038/s44321-024-00090-6. https://pubmed.ncbi.nlm.nih.gov/38926633/

3. Zhao, Rui, Tian, Linli, Zhao, Bo, Shang, Desi, Liu, Ming. 2020. FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling. In Cell death & disease, 11, 272. doi:10.1038/s41419-020-2457-5. https://pubmed.ncbi.nlm.nih.gov/32332698/

4. Lu, Ying, Shao, Jing, Shu, Xu, Lai, Yongkang, Liu, Ji. . FADS1 is a Prognostic Biomarker in Bladder Cancer: A Study Based on TCGA Data. In Combinatorial chemistry & high throughput screening, 24, 1197-1204. doi:10.2174/1386207323666200925104911. https://pubmed.ncbi.nlm.nih.gov/32981498/