Lipid Metabolic Key Drivers of Proliferation and Differentiation in Oral Squamous Cell Carcinoma: A Review

The development and progression of oral squamous cell carcinoma (OSCC) are significantly influenced by lipid metabolism, which undergoes metabolic reprogramming to meet the increased energy demands required for rapid invasion, proliferation, and metastasis. Dysregulated lipid metabolism-including alterations in fatty acid production, cholesterol homeostasis, and lipid oxidation- has been identified as a major factor in tumor development. In OSCC, lipid oxidation provides sustained energy for the long-term growth of hypoxic tumors, while FASN-mediated fatty acid synthesis supports membrane production in rapidly proliferating tongue squamous cell carcinoma. Furthermore, cholesterol metabolism influences immune evasion and oncogenic signalling by modulating key cellular pathways. Recent research has shown that Fatty Acid Synthase (FASN), Sterol Regulatory Element Binding Proteins (SREBPs), Fatty Acid Binding Proteins (FABPs), and CD36 (Cluster of Differentiation 36) act as key regulators of lipid reprogramming in OSCC. Dysfunctional lipid metabolic reprogramming mediated by these regulators contributes to enhanced drug resistance and activation of pro-inflammatory pathways within the tumour microenvironment, thereby supporting tumour growth and progression. Understanding the interactions between lipid metabolism and carcinogenic pathways may enable the development of novel therapeutic options by targeting metabolic vulnerabilities in OSCC. This review explains the molecular mechanisms underlying lipid metabolism in oral cancer and highlights its potential as a biomarker for disease progression. By focusing on lipid metabolism, new therapeutic strategies could be developed to improve the effectiveness of existing treatments and ultimately enhance the prognosis for patients with OSCC.