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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Chantôme A,Potier-Cartereau M,Clarysse L,Fromont G,Marionneau-Lambot S,Guéguinou M,Pagès JC,Collin C,Oullier T,Girault A,Arbion F,Haelters JP,Jaffrès PA,Pinault M,Besson P,Joulin V,Bougnoux P,Vandier C

doi

10.1158/0008-5472.CAN-12-4572

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

4852-61

issue

15

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-12-4572

journal_volume

73

pub_type

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