Soat1-KO Mouse

SOAT1, also known as acyl-coenzyme A (CoA):cholesterol acyltransferase 1 (ACAT1), is a key enzyme in lipid metabolism. It mediates cholesterol esterification, converting cholesterol to cholesterol esters for storage in lipid droplets. This process is crucial for maintaining cholesterol homeostasis, and it is associated with pathways such as the mevalonate pathway [2]. Cholesterol homeostasis is vital for various biological processes, including cell membrane integrity, signaling, and lipid droplet formation, and thus SOAT1 is of great biological importance. Genetic models, like KO or CKO mouse models, can significantly contribute to understanding its functions.

In pancreatic cancer, genetic targeting of Soat1 in p53 mutant cells that have undergone p53 loss of heterozygosity (LOH) impairs cell proliferation in vitro and tumor progression in vivo, revealing a mevalonate pathway dependency [2]. In hepatocellular carcinoma, SOAT1 promotes epithelial-mesenchymal transition (EMT), cell migration, and invasion, accelerating tumorigenesis and development in xenograft and NAFLD-HCC models. Nootkatone, a sesquiterpene ketone, can inhibit EMT by targeting SOAT1 in vitro and in vivo [1]. In colorectal cancer, silencing SOAT1 strongly inhibits the migration and invasion ability of tumor cells, and high intratumor SOAT1 expression correlates with lymph node metastasis and poor patient survival [3].

In conclusion, SOAT1 is essential for maintaining cholesterol homeostasis and is involved in lipid metabolism. Through model-based research, especially KO/CKO mouse models in pancreatic and liver cancers, it has been shown to play a significant role in tumor progression. In colorectal cancer, its function in promoting metastasis has also been revealed. These findings emphasize the potential of SOAT1 as a therapeutic target in cancer treatment.

References:

1. Fu, Rongrong, Xue, Wenqing, Liang, Jingjie, Zhang, Min, Meng, Jing. 2024. SOAT1 regulates cholesterol metabolism to induce EMT in hepatocellular carcinoma. In Cell death & disease, 15, 325. doi:10.1038/s41419-024-06711-9. https://pubmed.ncbi.nlm.nih.gov/38724499/

2. Oni, Tobiloba E, Biffi, Giulia, Baker, Lindsey A, Vakoc, Christopher R, Tuveson, David A. . SOAT1 promotes mevalonate pathway dependency in pancreatic cancer. In The Journal of experimental medicine, 217, . doi:10.1084/jem.20192389. https://pubmed.ncbi.nlm.nih.gov/32633781/

3. Wang, Xin-Chun, Luo, Lin-Ming, Huang, Tao-Sheng, Feng, Li-Feng. 2021. SOAT1 is a new prognostic factor of colorectal cancer. In Irish journal of medical science, 191, 1549-1554. doi:10.1007/s11845-021-02746-5. https://pubmed.ncbi.nlm.nih.gov/34460058/