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The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.
Gueguinou, M; Crottès, D; Chantôme, A; Rapetti-Mauss, R; Potier-Cartereau, M; Clarysse, L; Girault, A; Fourbon, Y; Jézéquel, P; Guérin-Charbonnel, C; Fromont, G; Martin, P; Pellissier, B; Schiappa, R; Chamorey, E; Mignen, O; Uguen, A; Borgese, F; Vandier, C; Soriani, O.
Afiliação
  • Gueguinou M; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Crottès D; Université Côte d'Azur, CNRS, Inserm, iBV, France.
  • Chantôme A; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Rapetti-Mauss R; Université Côte d'Azur, CNRS, Inserm, iBV, France.
  • Potier-Cartereau M; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Clarysse L; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Girault A; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Fourbon Y; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Jézéquel P; Unité de Bioinfomique, Institut de Cancérologie de L'Ouest - René Gauducheau, Centre de Recherche en Cancérologie, UMR-INSERM 892, St Herblain, France.
  • Guérin-Charbonnel C; Unité de Bioinfomique, Institut de Cancérologie de L'Ouest - René Gauducheau, Centre de Recherche en Cancérologie, UMR-INSERM 892, St Herblain, France.
  • Fromont G; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
  • Martin P; Service d'Anatomie Pathologique, Hopital Bretonneau, CHRU Tours, Tours, France.
  • Pellissier B; Université Côte d'Azur, CNRS, Inserm, iBV, France.
  • Schiappa R; Université Côte d'Azur, CNRS, Inserm, iBV, France.
  • Chamorey E; Unité d'Epidémiologie et Biostatistiques (UEB), Centre Antoine Lacassagne, Nice, France.
  • Mignen O; Unité d'Epidémiologie et Biostatistiques (UEB), Centre Antoine Lacassagne, Nice, France.
  • Uguen A; Department of Pathology, Inserm U1078, Brest University Hospital, Brest, France.
  • Borgese F; Department of Pathology, Inserm U1078, Brest University Hospital, Brest, France.
  • Vandier C; Université Côte d'Azur, CNRS, Inserm, iBV, France.
  • Soriani O; Inserm-University U1069 Nutrition, Croissance et Cancer, Tours, France.
Oncogene ; 36(25): 3640-3647, 2017 06 22.
Article em En | MEDLINE | ID: mdl-28114279
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Neoplasias Colorretais / Movimento Celular / Receptores sigma / Sinalização do Cálcio / Canais de Potássio Ativados por Cálcio de Condutância Baixa / Proteínas de Neoplasias Limite: Female / Humans / Male Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Neoplasias Colorretais / Movimento Celular / Receptores sigma / Sinalização do Cálcio / Canais de Potássio Ativados por Cálcio de Condutância Baixa / Proteínas de Neoplasias Limite: Female / Humans / Male Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: França