Tumor cell membranes have multiple components that participate in the process of metastasis. The present study investigates the physical association of β1-integrins and Kv1.3 voltage-gated potassium channels in melanoma cell membranes using resonance energy transfer (RET) techniques. RET between donor-labeled anti–β1-integrin and acceptor-labeled anti-Kv1.3 channels was detected on LOX cells adherent to glass and fibronectin-coated coverslips. However, RET was not observed on LOX cells in suspension, indicating that molecular proximity of these membrane molecules is adherence-related. Several K+ channel blockers, including tetraethylammonium, 4-aminopyridine, and verapamil, inhibited RET between β1-integrins and Kv1.3 channels. However, the irrelevant K+ channel blocker apamin had no effect on RET between β1-integrins and Kv1.3 channels. Based on these findings, we speculate that the lateral association of Kv1.3 channels with β1-integrins contributes to the regulation of integrin function and that channel blockers might affect tumor cell behavior by influencing the assembly of supramolecular structures containing integrins
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