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

Aurélie Chantôme 1 Marie Potier-Cartereau 2 Lucie Clarysse 2 Gaëlle Fromont 3 Séverine Marionneau-Lambot 4 Maxime Guéguinou 2 Jean-Christophe Pagès 5, 6 Christine Collin 5, 6 Thibauld Oullier 4 Alban Girault 2 Flavie Arbion 7 Jean-Pierre Haelters 8 Paul-Alain Jaffres 8 Michelle Pinault 2 Pierre Besson 2 Virginie Joulin 9 Philippe Bougnoux 2, 6 Christophe Vandier 2
1 Inserm UMR1069
N2C - Nutrition, croissance et cancer
2 N2C - Nutrition, croissance et cancer
3 Service d'Anatomie et de Cytologie Pathologiques [Poitiers]
4 Cancéropôle du Grand Ouest
5 Virus, pseudo-virus: Morphogénèse et Antigénicité
6 Hôpital Bretonneau
7 Service d'Anatomopathologie [Tours]
8 CEMCA - Chimie, Electrochimie Moléculaires et Chimie Analytique
9 Hématopoïèse normale et pathologique
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.
Type de document :
Article dans une revue
Cancer Research, American Association for Cancer Research, 2013, epub ahead of print. 〈10.1158/0008-5472.CAN-12-4572〉
Liste complète des métadonnées
http://www.hal.inserm.fr/inserm-00848873
Contributeur : Christophe Vandier <>
Soumis le : lundi 29 juillet 2013 - 14:21:35
Dernière modification le : jeudi 5 avril 2018 - 10:36:50

Lien texte intégral

openaccess

Identifiants

Collections

UNIV-NANTES | UNIV-POITIERS | IGR | FNCLCC | UNIV-BREST | INC-CNRS | CEMCA-BREST

Citation

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〉

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

624

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD