Choline Transport Mechanisms in Cancer and Neurological Disorders
Summary
Choline is a quaternary ammonium compound essential for membrane phospholipid synthesis, methyl-group donation and acetylcholine production. As a charged molecule, choline relies on specialised transport proteins to traverse plasma and organelle membranes. In cancer cells, elevated choline uptake supports rapid membrane biogenesis and oncogenic signalling, with choline transporter-like protein 1 (CTL1) often overexpressed and emerging as a therapeutic target. Inhibitors of CTL1 curb tumour growth by disrupting phosphatidylcholine synthesis and inducing ceramide-mediated apoptosis. Parallel investigations have revealed mitochondrial carriers such as SLC25A48 that import choline into mitochondria, linking organelle metabolism to cellular homeostasis.
Within the nervous system, high-affinity choline transporters at the blood–brain barrier and neuronal synapses ensure a steady supply of substrate for acetylcholine synthesis. Distinct transporter families—including the high-affinity CHT1, intermediate-affinity CTL1 and CTL2 proteins, and low-affinity organic cation transporters—operate in concert to regulate choline distribution between endothelial cells, astrocytes and neurons. Dysregulation of these pathways has been implicated in neurodegenerative disorders such as Alzheimer’s disease, where impaired choline uptake compromises cholinergic transmission. Understanding these transport mechanisms offers new avenues for neuromodulation and targeted interventions in both oncology and neurology.
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Choline Transport Mechanisms in Cancer and Neurological Disorders publication trend
The graph below shows the total number of articles in choline transport mechanisms in cancer and neurological disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Choline transporter-like protein 1 (CTL1): A membrane carrier that mediates intermediate-affinity choline uptake for phosphatidylcholine synthesis and signalling.
High-affinity choline transporter 1 (CHT1): A sodium-dependent transporter in cholinergic neurons responsible for rapid choline uptake into presynaptic terminals.
Organic cation transporters (OCTs): Low-affinity, polyspecific carriers (OCT1–3) that transport a range of organic cations, including choline, across cell membranes.
Phosphatidylcholine: The predominant phospholipid in eukaryotic cell membranes, synthesised via the CDP-choline (Kennedy) pathway.
Ceramide: A lipid second messenger generated upon disruption of choline metabolism, which can trigger apoptotic signalling in cancer cells.
References
- The membrane transporter SLC25A48 enables transport of choline into human mitochondria. Kidney International (2024).
- Functional Expression of Choline Transporters in the Blood–Brain Barrier. Nutrients (2019).
- Molecular and Functional Analysis of Choline Transporters and Antitumor Effects of Choline Transporter-Like Protein 1 Inhibitors in Human Pancreatic Cancer Cells. International Journal of Molecular Sciences (2020).
- Anticancer Activity of Amb4269951, a Choline Transporter-Like Protein 1 Inhibitor, in Human Glioma Cells. Pharmaceuticals (2020).
- A Novel Plant-Derived Choline Transporter-like Protein 1 Inhibitor, Amb544925, Induces Apoptotic Cell Death via the Ceramide/Survivin Pathway in Tongue Squamous Cell Carcinoma. Cancers (2022).
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