Pivotal Role of the Lipid Raft SK3-Orai1 Complex in Human Cancer Cell Migration and Bone Metastases.

Abstract : : The SK3 channel, a potassium channel, was recently shown to control cancer cell migration, a critical step in metastasis outgrowth. Here, we report that expression of the SK3 channel was markedly associated with bone metastasis. The SK3 channel was shown to control constitutive Ca(2+) entry and cancer cell migration through an interaction with the Ca(2+) channel Orai1. We found that the SK3 channel triggers an association with the Orai1 channel within lipid rafts. This localization of an SK3-Orai1 complex seemed essential to control cancer cell migration. This suggests that the formation of this complex in lipid rafts is a gain-of-function, because we showed that none of the individual proteins were able to promote the complete phenotype. We identified the alkyl-lipid Ohmline as a disrupting agent for SK3-Orai1 lipid raft localization. Upon Ohmline treatment, the SK3-Orai1 complex moved away from lipid rafts, and SK3-dependent Ca(2+) entry, migration, and bone metastases were subsequently impaired. The colocalization of SK3 and Orai1 in primary human tumors and bone metastases further emphasized the clinical relevance of our observations. Targeting SK3-Orai1 in lipid rafts may inaugurate innovative approaches to inhibit bone metastases. Cancer Res; 73(15); 1-10. ©2013 AACR.
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Cancer Research, American Association for Cancer Research, 2013, epub ahead of print. 〈10.1158/0008-5472.CAN-12-4572〉
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Soumis le : lundi 29 juillet 2013 - 14:21:35
Dernière modification le : jeudi 11 janvier 2018 - 06:17:06

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Aurélie Chantôme, Marie Potier-Cartereau, Lucie Clarysse, Gaëlle Fromont, Séverine Marionneau-Lambot, et al.. Pivotal Role of the Lipid Raft SK3-Orai1 Complex in Human Cancer Cell Migration and Bone Metastases.. Cancer Research, American Association for Cancer Research, 2013, epub ahead of print. 〈10.1158/0008-5472.CAN-12-4572〉. 〈inserm-00848873〉

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