SOAT1, also known as acyl-coenzyme A (CoA):cholesterol acyltransferase 1 (ACAT1), is a key enzyme in lipid metabolism. It localizes in the endoplasmic reticulum and mediates cholesterol esterification, converting cholesterol to cholesterol esters for storage in lipid droplets. This process is crucial for maintaining cholesterol homeostasis, which is involved in multiple biological pathways such as the mevalonate pathway [2,4]. Cholesterol homeostasis is vital for various cellular functions, including adipocyte function and cell membrane integrity [4]. Genetic models, like gene-knockout (KO) mouse models, have been valuable for studying SOAT1's functions.

In pancreatic cancer, genetic targeting of Soat1 in mouse models impairs cell proliferation in vitro and tumor progression in vivo, revealing a mevalonate pathway dependency in p53 mutant PDAC cells with p53 loss of heterozygosity (LOH) [2]. In hepatocellular carcinoma, SOAT1 promotes epithelial-mesenchymal transition (EMT) and tumorigenesis. Nootkatone, which targets SOAT1, can inhibit EMT in vitro and in vivo [1]. In colorectal cancer, silencing SOAT1 in cell lines strongly inhibits the migration and invasion ability of CRC tumor cells, indicating its role in promoting cancer progression [3]. In gastric cancer, knockdown of SOAT1 or its pharmacological inhibition suppresses cell proliferation, cholesterol ester synthesis, and lymphangiogenesis, while overexpression promotes these processes [5].

In conclusion, SOAT1 plays essential roles in lipid metabolism, especially in maintaining cholesterol homeostasis. Through KO or related mouse models, it has been shown to significantly influence the development and progression of multiple cancers, including pancreatic, hepatocellular, colorectal, and gastric cancers. Understanding SOAT1's functions in these disease contexts provides potential therapeutic targets for cancer treatment.