Choline Metabolism and Phospholipid Dynamics in Cancer Systems
Summary
Cancer cells commonly remodel their choline uptake and utilisation to sustain rapid proliferation, migration and survival. Central to this remodelling is the Kennedy pathway, which converts free choline into phosphocholine and ultimately into phosphatidylcholine, the predominant membrane phospholipid. Aberrant activity of choline kinase, phospholipases and choline transporters leads to elevated phosphocholine pools, altered membrane composition and production of bioactive lipid mediators that drive oncogenic signalling, therapy resistance and immune evasion. These phospholipid dynamics intersect with energy metabolism, endoplasmic reticulum stress responses and the tumour microenvironment, giving rise to metabolic vulnerabilities that can be exploited by inhibitors, imaging probes and combination treatments. Advances in metabolomic profiling and molecular biology have illuminated the interplay between membrane biogenesis and lipid-mediated communication, highlighting global significance for diagnosis, prognostication and tailored therapies across diverse cancer types.
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Choline Metabolism and Phospholipid Dynamics in Cancer Systems publication trend
The graph below shows the total number of articles in choline metabolism and phospholipid dynamics in cancer systems across all publications each year (not limited to Nature Index journals).
Technical terms
Kennedy pathway: Metabolic route converting choline into phosphatidylcholine via phosphocholine intermediates.
Choline kinase α (ChoKα): Enzyme that phosphorylates free choline to phosphocholine, initiating phosphatidylcholine synthesis.
Phosphatidylcholine (PC): Major phospholipid of eukaryotic membranes, involved in structural integrity and signalling.
Phospholipid dynamics: Processes governing synthesis, turnover and signalling roles of membrane lipids in cells.
Tumour microenvironment (TME): Complex milieu of stromal cells, immune cells and extracellular matrix that interacts with cancer cells.
References
- Targeting Phospholipid Metabolism in Cancer. Frontiers in Oncology (2016).
- The Tumor Microenvironment Modulates Choline and Lipid Metabolism. Frontiers in Oncology (2016).
- Positron Emission Tomography Imaging of Tumor Cell Metabolism and Application to Therapy Response Monitoring. Frontiers in Oncology (2016).
- Inhibition of choline metabolism in an angioimmunoblastic T-cell lymphoma preclinical model reveals a new metabolic vulnerability as possible target for treatment. Journal of Experimental & Clinical Cancer Research (2024).
- Choline metabolism reprogramming mediates an immunosuppressive microenvironment in non-small cell lung cancer (NSCLC) by promoting tumor-associated macrophage functional polarization and endothelial cell proliferation. Journal of Translational Medicine (2024).
- Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells. Frontiers in Immunology (2022).
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