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The potassium channel SK3 may be a regulator of bone metastasis



DOI:10.1038/bonekey.2013.200

Ion channel regulators are emerging as an important class of molecules that regulate cancer metastasis. Chantôme et al. investigated the possible role of SK3, a member of the calcium-activated class of potassium channels.

Breast cancer cells with luciferase-labeled SK3 were treated with shRNA specific for the KCNN3 gene to produce a specific SK3 knockdown. SK3− cells had a more depolarized membrane, showed little outward current and an impaired migration capacity, but proliferated normally.

In an NMRI nude mouse xenograft model, SK3− cells had fewer metastases in bone and lung tissue. Although the bioluminescence signal in lung metastases was equivalent in SK3− treated mice and controls, the signal per metastasis in bone tissue was significantly lower in SK3− treated mice vs controls.

SK3 appeared to increase migration of cancer cells to bone in response to a rise in intracellular calcium (Ca2+), mediated by increased activity of the calcium-sensitive protease calpain. The calcium channel responsible for Ca2+ entry was Orai1, a voltage-independent Ca2+ channel. The SK3/Orai1 complex was localized by immunofluorescence to lipid rafts in the plasma membrane.

Editor’s comment: This is the first report demonstrating that a molecular complex within lipid rafts consisting of a potassium channel (SK3) and a voltage-independent calcium channel (Orai1) promotes the formation of metastasis of breast cancer to bone. The report also opens up new avenues for developing therapies to target lipid rafts and so inhibit bone metastases.


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