The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis

被引：91

作者：

Gueguinou, M. ^{[1
,7
]}

Crottes, D. ^{[2
]}

Chantome, A. ^{[1
,7
]}

Rapetti-Mauss, R. ^{[2
]}

Potier-Cartereau, M. ^{[1
,7
]}

Clarysse, L. ^{[1
,7
]}

Girault, A. ^{[1
,7
]}

Fourbon, Y. ^{[1
,7
]}

Jezequel, P. ^{[3
]}

Guerin-Charbonnel, C. ^{[3
]}

Fromont, G. ^{[1
,4
,7
]}

Martin, P. ^{[2
]}

Pellissier, B. ^{[2
]}

Schiappa, R. ^{[5
]}

Chamorey, E. ^{[5
]}

Mignen, O. ^{[6
,7
]}

Uguen, A. ^{[6
]}

Borgese, F. ^{[2
]}

Vandier, C. ^{[1
,7
]}

Soriani, O. ^{[2
]}

机构：

[1] Univ Tours, INSERM, U1069, Nutr Croissance & Canc, Tours, France

[2] Univ Cote Azur, INSERM, CNRS, iBV, Nice, France

[3] INSERM, UMR 892, Ctr Rech Cancerol, Unit Bioinfom,Inst Cancerol Ouest Rene Gauducheau, St Herblain, France

[4] CHRU Tours, Hop Bretonneau, Serv Anat Pathol, Tours, France

[5] Ctr Antoine Lacassagne, UEB, Nice, France

[6] Brest Univ Hosp, INSERM, U1078, Dept Pathol, Brest, France

[7] Ion Channels & Canc Canceropole Grand Ouest IC CG, Brest, France

来源：

ONCOGENE | 2017年 / 36卷 / 25期

关键词：

ELECTRICAL-ACTIVITY; RECEPTOR; CHANNEL; PLASTICITY; ROLES; INHIBITION; MECHANISM; RESPONSES; MEMBRANE; COMPLEX;

D O I：

10.1038/onc.2016.501

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca2+-activated K+ channel (KCNN3) and the voltage- independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca2+ homeostasis in epithelial cancers.

引用

页码：3640 / 3647

页数：8

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