Copper transporter 1 (CTR1) (CTR1)

Copper transporter 1 (CTR1), encoded by the SLC31A1 gene, is the primary high-affinity integral membrane protein responsible for the cellular uptake of dietary copper and platinum-based chemotherapeutic agents like cisplatin (UniProt: P44673). It functions as a homotrimer, forming a pore that allows the passive but gated transport of metal ions across the plasma membrane (PubMed: 16155133). The activity and membrane density of CTR1 are significantly influenced by the Sodium/potassium-transporting ATPase (Na+,K+-ATPase), which physically interacts with CTR1 and regulates its trafficking and stability (PubMed: 24652556). In many cancers, the downregulation or internal sequestration of CTR1 is a major mechanism of acquired resistance to cisplatin therapy (PubMed: 21135114). Conversely, pharmacological modulation of the Na+,K+-ATPase, for instance by cardiotonic steroids like ouabain, can trigger CTR1 endocytosis, thereby reducing cisplatin uptake and making this interaction a focal point for overcoming drug resistance (PubMed: 22431509). This regulatory axis is also implicated in the side effects of platinum drugs, as CTR1-mediated uptake in the kidneys and inner ear contributes to nephrotoxicity and ototoxicity (PubMed: 19435911). Understanding this synergy is crucial for optimizing platinum-based regimens and developing sensitizing agents in oncology. Research continues to explore how targeting the Na+,K+-ATPase/CTR1 complex can improve the therapeutic index of platinum drugs.

Other names

SLC31A1Solute carrier family 31 member 1High affinity copper transporter 1COPT1High affinity copper uptake protein 1

CTR1 facilitates the transmembrane influx of platinum-based drugs into the cytoplasm. The Sodium/potassium-transporting ATPase (Na+,K+-ATPase) regulates this process by physically interacting with CTR1, ensuring its stability and localization on the plasma membrane; inhibition of the ATPase leads to CTR1 internalization and reduced drug uptake.