Lipid homeostasis dysregulation in oral cancer drives metabolic reprogramming and offers novel diagnostic and therapeutic opportunities

作者：Liang Liang, Chen Luo, Shuo Dong, Zhe Jia, Linyu Zhao, Jingchao Tang, Min Li, Xiaoren Zong, Simin Li, Zuryati Ab‐Ghani · 发表于：Discover Oncology · 年份：2025 · DOI：10.1007/s12672-025-03299-0 · 被引用次数：6 · 研究领域：Cancer, Lipids, and Metabolism、Cancer, Hypoxia, and Metabolism、Peroxisome Proliferator-Activated Receptors

Oral cancer remains a significant global health challenge, with oral squamous cell carcinoma (OSCC) being the predominant histological type. Recent research has highlighted the critical role of metabolic reprogramming in oral carcinogenesis, particularly alterations in lipid homeostasis that contribute to disease progression and development. This review synthesizes current knowledge on lipid metabolism dysregulation in oral cancer, focusing on key aspects of metabolic reprogramming mechanisms, serum lipid profile alterations, lipid peroxidation pathways, immunometabolic interactions, and emerging therapeutic strategies. Mechanistically, OSCC exhibits significant alterations in key lipid metabolic enzymes, including upregulation of fatty acid synthase and ATP citrate lyase, and downregulation of carboxylesterase 2 (CES2), collectively promoting tumor growth and metastasis. These enzymatic changes are orchestrated through complex signaling pathways, notably the PI3K/AKT/mTOR axis, and manifest in altered membrane lipid composition, particularly within lipid microdomains that influence both cell signaling and drug resistance. Clinically, OSCC patients demonstrate characteristic serum lipid profile alterations, including reduced levels of total cholesterol, high-density lipoprotein cholesterol, and specific apolipoproteins, which show promise as non-invasive biomarkers for early detection and prognosis. Furthermore, enhanced lipid peroxidation through reactive oxygen species pres...