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The roles of K+ channels in cancer

Key Points

  • Ion transport molecules are involved in many physiological and pathological processes.

  • Among ion transporters, potassium channels show the highest variability and the most frequently altered expression in many tumour types.

  • Cell cycle and proliferation, cell migration, invasion and apoptosis are all processes that can be modified by the expression of potassium channels.

  • Permeation-dependent and permeation-independent mechanisms contribute to the roles of potassium channels in oncological processes.

  • The experience gained with pharmacological manipulation of potassium channels in other pathologies might facilitate the use of potassium channels as cancer targets.

Abstract

Potassium channels are transmembrane proteins that selectively facilitate the flow of potassium ions down an electrochemical gradient. These molecules have been studied in great detail in the context of cell excitability, but their roles in less cell type-specific functions, such as cell proliferation, angiogenesis or cell migration, have only recently been assessed. Moreover, the importance of these channels for tumour biology has become evident. This, coupled with the fact that they are accessible proteins and that their pharmacology is well characterized, has increased the interest in investigating potassium channels as therapeutic targets in cancer patients.

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Figure 1: Schematic structure of potassium channels.
Figure 2: Summary of the roles of K+ channels in oncology and the mechanisms responsible for their aberrant expression.
Figure 3: Summary of the roles of Kv10.1 in oncology and the mechanisms that are responsible for its aberrant expression in tumour cells.

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Acknowledgements

The authors thank the Max Planck Society and the past and present members of their department.

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Correspondence to Luis A. Pardo or Walter Stühmer.

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L.A.P. and W.S. are shareholders of iOnGen AG.

PowerPoint slides

Glossary

Permeation path

The path formed by a fourfold repeat of the pore-forming loop (P-loop) that is provided by each of the four subunits that constitutes the ion channel. Residues in the P-loop are responsible for the selectivity for specific ions.

Fratricide

The induction of apoptotic death in nearby cells, which normally occurs via a death receptor and its ligand. This occurs naturally in the immune system and other systems, and it can also be induced by chimeric ligands.

Long QT syndrome

The prolongation of the ventricular action potential, which can be diagnosed by a large time interval between the Q and T waves in an electrocardiogram. It is mainly caused by genetic mutations in mechanisms that are responsible for repolarization, such as the Kv11.1-related ion channel ERG.

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Pardo, L., Stühmer, W. The roles of K+ channels in cancer. Nat Rev Cancer 14, 39–48 (2014). https://doi.org/10.1038/nrc3635

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