Pivotal Role of the Lipid Raft SK3-Orai1 Complex in Human Cancer Cell Migration and Bone Metastases. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Cancer Research Year : 2013

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

Thibauld Oullier

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.

Domains

Cancer

Dates and versions

inserm-00848873 , version 1 (29-07-2013)

Identifiers

Cite

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, 2013, epub ahead of print. ⟨10.1158/0008-5472.CAN-12-4572⟩. ⟨inserm-00848873⟩
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