Lipid Metabolism in Oral and Head Neck Cancer

Cancerous cells of the oral cavity and head and neck region exhibit profound remodelling of lipid pathways to support rapid proliferation, invasion and survival within a hostile microenvironment. Enhanced de novo lipogenesis supplies fatty acids for membrane biogenesis, while upregulation of fatty acid oxidation (FAO) provides ATP under fluctuating nutrient and oxygen levels. Cholesterol homeostasis is similarly perturbed, with increased synthesis and uptake contributing to the formation of lipid rafts that concentrate pro-oncogenic receptors. Key enzymes such as fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT1) are frequently overexpressed, correlating with tumour grade and poor outcome. Beyond bioenergetics and structural roles, lipid intermediates act as signalling mediators that modulate pathways governing epithelial–mesenchymal transition, angiogenesis and immune evasion. Advances in mass-spectrometry-based lipidomics have revealed tumour-specific signatures of glycerophospholipids, sphingolipids and cholesterol esters, offering both mechanistic insights and potential biomarkers. Therapeutic strategies that target lipid enzymes or exploit metabolic vulnerabilities are under investigation, with the aim of enhancing the efficacy of standard modalities and overcoming resistance.

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Lipid Metabolism in Oral and Head Neck Cancer publication trend

The graph below shows the total number of articles in lipid metabolism in oral and head neck cancer across all publications each year (not limited to Nature Index journals).

Technical terms

De novo lipogenesis: Enzymatic conversion of acetyl-CoA into fatty acids for membrane synthesis and signalling.

Fatty acid oxidation (FAO): Mitochondrial pathway that degrades fatty acids to generate ATP under metabolic stress.

Lipid rafts: Cholesterol‐ and sphingolipid‐rich microdomains in the plasma membrane that cluster signalling molecules.

Lipidomics: Comprehensive analysis of cellular lipid species by high‐throughput mass spectrometry.

Caveolin-1 (CAV1): Membrane protein that binds cholesterol, influences raft stability and regulates cell migration.

Nomogram: Statistical tool that integrates multiple variables, including biomarkers, to predict individual patient outcomes.

References

1. Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences (2023).
2. The Prognostic Value of Preoperative Total Cholesterol in Surgically Treated Oral Cavity Cancer. Biomedicines (2024).
3. Prognostic Value of the Overexpression of Fatty Acid Metabolism-Related Enzymes in Squamous Cell Carcinoma of the Head and Neck. International Journal of Molecular Sciences (2020).