Scd1-flox Mouse

Scd1, or stearoyl-CoA desaturase 1, is a key enzyme in lipid metabolism. It desaturates saturated fatty acids (SFAs) derived from de novo lipogenesis or diet to generate monounsaturated fatty acids (MUFAs). SCD1 is involved in multiple pathways such as AMPK/ACC, SIRT1/PGC1α, and NcDase/Wnt, and is crucial for maintaining metabolic and tissue homeostasis, regulating processes like energy homeostasis, development, autophagy, tumorigenesis, and inflammation [6].

In cancer, SCD1 promotes cell proliferation and metastasis. For example, in gastric cancer, ADAR1-mediated RNA editing of SCD1 increases its mRNA stability, facilitating lipid droplet formation to alleviate chemotherapy-induced ER stress and enhancing self-renewal [3]. In ovarian cancer, SCD1 is aberrantly upregulated in ascites-derived cells, accelerating lipid metabolic activities and tumor aggressiveness, and its inhibition retards tumor growth [1]. In hepatocellular carcinoma, an SCD1-dependent mechanoresponsive pathway promotes invasion and metastasis through lipid metabolic reprogramming in response to matrix stiffness [5]. In colorectal cancer, TIGAR drives ferroptosis resistance via the ROS/AMPK/SCD1 pathway [8], and aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutant cells [7]. Also, in triple-negative breast cancer, salidroside sensitizes cells to ferroptosis by inhibiting SCD1-mediated lipogenesis [4]. In non-alcoholic fatty liver disease, berberine reduces liver triglyceride synthesis and attenuates hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway [2]. Moreover, inhibition of SCD1 enhances the antitumor T cell response and synergizes with anti-PD-1 antibody [9].

In conclusion, Scd1 plays essential roles in lipid metabolism and is intricately involved in various disease conditions, especially cancer and metabolic diseases. Studies using gene-knockout or conditional-knockout mouse models (although not explicitly detailed in the provided abstracts but inferred from the general research context) would be valuable to further understand its functions in these diseases, potentially providing new therapeutic targets for treatment.