Fatty Acid Metabolism in Cancer Cell Dynamics

Cancer cells often rewire their lipid metabolism to support rapid proliferation, survival under stress and metastatic spread. Enhanced uptake of extracellular fatty acids, increased de novo lipogenesis and altered β-oxidation converge to supply energy, membrane components and signalling lipids. Central to this rewiring are fatty acid-binding proteins (FABPs) that shuttle long-chain fatty acids to metabolic enzymes or nuclear receptors, and peroxisome proliferator-activated receptors (PPARs) that transcriptionally link lipid flux to cell growth programmes. Hypoxia-inducible factor-1 (HIF-1) further integrates oxygen status with lipid homeostasis, promoting lipid droplet formation and adaptation to low-oxygen niches. Downstream effects include promotion of epithelial–mesenchymal transition, activation of inflammatory pathways such as NF-κB, and resistance to chemotherapy. By exploiting metabolic plasticity, cancer cells gain a survival advantage in diverse microenvironments, making fatty acid metabolism a promising target for novel anticancer strategies.

Research from Nature Portfolio

Recent studies have identified fatty acid-binding protein 5 (FABP5) as a regulator of lipid-driven inflammation and tumour growth dynamics in malignant pleural mesothelioma. Elevated myristic, palmitic and stearic acid levels in tumour cells engage FABP5 to modulate NF-κB signalling, driving proliferation and apoptosis resistance. In parallel, a pan-cancer analysis has delineated how FABP5 overexpression correlates with poor prognosis across multiple tumour types. This work uncovers miRNA-mediated regulatory networks governing FABP5 expression and highlights links between FABP5 and immune checkpoint modulation. Foundational research in hepatocellular carcinoma has further shown that fatty acid-induced upregulation of FABP5 enhances HIF-1α activity, reprogramming lipid metabolism to promote lipid accumulation and cell proliferation under hypoxic conditions. Together, these findings underscore a central role for FABP5 as a mediator of lipid-dependent transcriptional programmes in diverse cancers.

Fatty Acid Metabolism in Cancer Cell Dynamics publication trend

The graph below shows the total number of articles in fatty acid metabolism in cancer cell dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Fatty acid-binding proteins (FABPs): Intracellular carriers that bind long-chain fatty acids and deliver them to metabolic enzymes or nuclear receptors.

De novo lipogenesis: The enzymatic synthesis of fatty acids from acetyl-CoA precursors, often upregulated in proliferating cells.

β-oxidation: The mitochondrial breakdown of fatty acids to generate acetyl-CoA and ATP.

Epithelial–mesenchymal transition (EMT): A process by which epithelial cells acquire motile and invasive properties, facilitating metastasis.

Peroxisome proliferator-activated receptors (PPARs): Nuclear hormone receptors that regulate genes involved in lipid metabolism, energy homeostasis and inflammation.

Hypoxia-inducible factor-1 (HIF-1): A transcription factor activated under low oxygen that reprogrammes metabolism to support cell survival in hypoxic environments.

References

1. FABP5 is a key player in metabolic modulation and NF-κB dependent inflammation driving pleural mesothelioma. Communications Biology (2025).
2. Doxorubicin resistance in breast cancer is mediated via the activation of FABP5/PPARγ and CaMKII signaling pathway. Frontiers in Pharmacology (2023).
3. Oncogenic role and potential regulatory mechanism of fatty acid binding protein 5 based on a pan-cancer analysis. Scientific Reports (2023).
4. FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism. Theranostics (2020).
5. Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells. Communications Biology (2020).