Fads2-KO Mouse

Fads2, also known as acyl-CoA 6-desaturase, is a key enzyme in long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis [4]. It catalyzes the biosynthesis of several unsaturated fatty acids through Δ6, Δ8, and Δ4 desaturation, playing a crucial role in fatty acid metabolism and being involved in pathways related to lipid metabolism and redox regulation [2]. Dysregulation of Fads2 has implications for various biological processes and diseases.

In cancer research, genetic ablation of Fads2 in ascites-derived ovarian cancer cells retarded tumor growth, cancer stem cell formation, and reduced platinum resistance. It also caused disruption of the cellular/mitochondrial redox balance, leading to iron-mediated lipid peroxidation and mitochondrial dysfunction [1]. In cholangiocarcinoma, Fads2 depletion reduced in vivo tumorigenicity, cell proliferation, migration, and sphere-forming ability, while increasing apoptotic cell death and ferroptosis markers. Lipidome assay showed decreased triglyceride and cholesterol ester levels in Fads2-knockdown cells [3].

In conclusion, Fads2 is essential for fatty acid metabolism. Through gene-knockout studies in cancer models, it has been revealed that Fads2 plays a tumor-promoting role in ovarian and cholangiocarcinoma. Understanding the function of Fads2 in these disease contexts provides potential therapeutic targets for cancer treatment.

References:

1. Xuan, Yang, Wang, Huogang, Yung, Mingo Mh, Chan, Karen Kl, Chan, David W. 2022. SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells. In Theranostics, 12, 3534-3552. doi:10.7150/thno.70194. https://pubmed.ncbi.nlm.nih.gov/35547771/

2. Kothapalli, Kumar S D, Park, Hui Gyu, Kothapalli, Niharika S L, Brenna, J Thomas. 2023. FADS2 function at the major cancer hotspot 11q13 locus alters fatty acid metabolism in cancer. In Progress in lipid research, 92, 101242. doi:10.1016/j.plipres.2023.101242. https://pubmed.ncbi.nlm.nih.gov/37597812/

3. Hasegawa, Kohsei, Fujimori, Haruna, Nakatani, Kohta, Katori, Yukio, Tamai, Keiichi. 2024. Delta-6 desaturase FADS2 is a tumor-promoting factor in cholangiocarcinoma. In Cancer science, 115, 3346-3357. doi:10.1111/cas.16306. https://pubmed.ncbi.nlm.nih.gov/39113435/

4. Bláhová, Zuzana, Harvey, Thomas Nelson, Pšenička, Martin, Mráz, Jan. 2020. Assessment of Fatty Acid Desaturase (Fads2) Structure-Function Properties in Fish in the Context of Environmental Adaptations and as a Target for Genetic Engineering. In Biomolecules, 10, . doi:10.3390/biom10020206. https://pubmed.ncbi.nlm.nih.gov/32023831/