CD36-Mediated Lipid Metabolism in Cancer Progression

CD36-mediated lipid metabolism has emerged as a central driver of cancer initiation, progression and metastasis. CD36, a transmembrane scavenger receptor, facilitates uptake of long-chain fatty acids and reshapes tumour bioenergetics by promoting fatty acid oxidation and lipid storage. Elevated CD36 expression in malignant cells activates oncogenic cascades—PI3K/AKT/mTOR, Wnt/β-catenin and TGF-β—enhancing proliferation, survival and migratory capacity. Simultaneously, CD36-dependent lipid handling in the tumour microenvironment, notably by macrophages and adipocytes, fosters immunosuppression and pre-metastatic niche formation. The convergence of these processes across diverse malignancies highlights CD36 as a compelling biomarker and therapeutic target in oncology.

Research from Nature Portfolio

Recent studies have elucidated multifaceted roles of CD36 within both cancer cells and stromal populations. In models of liver metastasis, upregulation of CD36 in metastasis-associated macrophages was shown to mediate uptake of tumour-derived fatty acid-rich vesicles, driving M2-like polarisation and reinforcing an immunosuppressive niche that supports metastatic colonisation. In colorectal cancer, foundational work revealed that CD36 interacts with glypican-4 to promote its ubiquitination and degradation, thereby inhibiting β-catenin/c-Myc signalling and glycolytic flux, which suppresses tumourigenesis. Seminal investigations in hepatocellular carcinoma demonstrated that CD36-dependent free fatty acid import triggers epithelial–mesenchymal transition through activation of Wnt and TGF-β pathways, offering mechanistic insight into metastatic dissemination.

CD36-Mediated Lipid Metabolism in Cancer Progression publication trend

The graph below shows the total number of articles in cd36-mediated lipid metabolism in cancer progression across all publications each year (not limited to Nature Index journals).

Technical terms

CD36: A membrane scavenger receptor that binds long-chain fatty acids and facilitates their cellular uptake, influencing energy metabolism and signalling.

Epithelial–mesenchymal transition (EMT): A cellular programme by which epithelial cells acquire mesenchymal properties, increasing motility and invasiveness.

Tumour microenvironment (TME): The complex milieu of stromal cells, immune infiltrates, extracellular matrix and signalling molecules surrounding tumour cells.

Palmitoylation: A reversible post-translational modification involving the covalent attachment of palmitic acid to specific cysteine residues on proteins, affecting their localisation and stability.

Fatty acid oxidation (FAO): The metabolic process by which fatty acids are broken down in mitochondria to generate acetyl-CoA, NADH and FADH₂ for energy production.

References

1. Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression. Cell Discovery (2023).
2. CD36 tango in cancer: signaling pathways and functions. Theranostics (2019).
3. Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma. Scientific Reports (2015).
4. CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis. Nature Communications (2019).
5. CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis. Nature Communications (2022).
6. The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis. Cell Death & Disease (2021).
7. Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer. npj Breast Cancer (2021).