Cholesterol acyltransferase-1: A novel diagnostic biomarker and potential therapeutic target for cancer

Aberrant lipid metabolism, particularly the dysregulation of cholesterol metabolism, is a hallmark of cancer cells, facilitating cancer progression. Targeting intracellular cholesterol homeostasis has emerged as a therapeutic strategy in cancer treatment. Esterification, a critical step for cholesterol storage, mitigates cytotoxicity induced by free cholesterol. Accumulation of cholesterol ester has been extensively revealed as a promoting factor for cancer progression. Elevated expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1), the primary enzyme responsible for cholesterol esterification, promotes cancer progression by activating multiple signaling pathways. ACAT-1 has garnered attention as a potential anti-cancer target, with many inhibitors developed and applied in cancer treatment. This review summarizes the effects and potential mechanisms of cholesterol ester accumulation on cancer cell proliferation, invasion, metastasis, chemotherapy resistance and immune evasion. Additionally, the role of ACAT-1 and the application of its inhibitors in various cancers are discussed, offering novel strategies for cancer therapy and diagnosis.