Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 48, Issue 6, Pages 2273-2285Publisher
KARGER
DOI: 10.1159/000492645
Keywords
Soce; Stim1; Orai1; Tumor; Multiple myeloma
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Funding
- Second Affiliated Hospital of Harbin Medical University
- Youth Science Fund of the Natural Science Foundation of China [81001051]
- Postdoctoral Science Foundation of China [2015M580270]
- Postdoctoral Science Foundation of Heilongjiang Province [LBH-Z15129]
- Young and middle-aged Science Foundation of Harbin Medical University [KYCX2018-15]
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Background/Aims: Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite the development and application of novel agents, MM still undergoes an aggressive and incurable course in the vast majority of patients. Ca2+ is one of the critical regulators of cell migration. Ca2+ influx is essential for the migration of various types of cells including tumor cells. However, the role of store-operated calcium entry (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been reported in MM cell survival. Methods: We evaluated the expression of Stim1 and Orai1 (two key regulators of SOC) in MM tissues and cell lines by immunohistochemical assay, quantitative real-time PCR assay and western blot. MM cell lines were pretreated with pharmacological blockers and siRNAs, and then MM cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the expression of Stim1 (or Orai1) level and outcome in MM were assessed by using Progress Free Survival (PFS). Results: Stim1 and Orai1 were both abundantly expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated with the clinical outcome of MM. Conclusion: The Stim1/Orai1-mediated signaling participates in the pathogenesis of MM, which represents an attractive target for future therapeutic intervention. (C) 2018 The Author(s) Published by S. Karger AG, Basel
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