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The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis
- Source :
- Oncogene, Oncogene, Nature Publishing Group, 2017, 36 (25), pp.3640-3647. ⟨10.1038/onc.2016.501⟩, Oncogene, 2017, 36 (25), pp.3640-3647. ⟨10.1038/onc.2016.501⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Colorectal cancer
[SDV]Life Sciences [q-bio]
chemistry.chemical_element
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Calcium
Biology
Molecular oncology
03 medical and health sciences
0302 clinical medicine
Internal medicine
Genetics
medicine
Molecular Biology
ComputingMilieux_MISCELLANEOUS
Calcium signaling
Calcium metabolism
ORAI1
Calcium channel
Bone metastasis
medicine.disease
3. Good health
030104 developmental biology
Endocrinology
chemistry
030220 oncology & carcinogenesis
Cancer research
Subjects
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Database :
- OpenAIRE
- Journal :
- Oncogene, Oncogene, Nature Publishing Group, 2017, 36 (25), pp.3640-3647. ⟨10.1038/onc.2016.501⟩, Oncogene, 2017, 36 (25), pp.3640-3647. ⟨10.1038/onc.2016.501⟩
- Accession number :
- edsair.doi.dedup.....27d9d3d986283646d1cbda663e6dae59