Abstract
Orai channels have been associated with cell proliferation, survival and metastasis in several cancers. The present study investigates the expression and the role of Orai3 in cell proliferation in non-small cell lung cancer (NSCLC). We show that Orai3 is over-expressed in cancer tissues as compared to the non-tumoral ones. Furthermore, Orai3 staining is stronger in high grade tumors. Pharmacological inhibition or knockdown of Orai3 significantly reduced store operated calcium entry (SOCE), inhibited cell proliferation and arrested cells of two NSCLC cell lines in G0/G1 phase. These effects were concomitant with a down-regulation of cyclin D1, cyclin E, CDK4 and CDK2 expression. Moreover, Orai3 silencing decreased Akt phosphorylation levels. In conclusion, Orai3 constitutes a native SOCE pathway in NSCLC that controls cell proliferation and cell cycle progression likely via Akt pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma of Lung
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Aged
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Calcium / metabolism
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Calcium Channels / genetics*
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Calcium Channels / metabolism
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Carcinoma, Non-Small-Cell Lung / genetics*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Line, Tumor
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Cell Proliferation
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Cyclin E / genetics
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Cyclin E / metabolism
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Cyclin-Dependent Kinase 2 / genetics
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Cyclin-Dependent Kinase 2 / metabolism
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Cyclin-Dependent Kinase 4 / genetics
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Cyclin-Dependent Kinase 4 / metabolism
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Female
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G1 Phase Cell Cycle Checkpoints
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Gene Expression Regulation, Neoplastic*
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Humans
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Lung Neoplasms / genetics*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Male
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Middle Aged
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Neoplasm Staging
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Phosphorylation
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Proto-Oncogene Proteins c-akt / genetics*
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Resting Phase, Cell Cycle
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Signal Transduction
Substances
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Calcium Channels
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Cyclin E
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Orai3 protein, human
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RNA, Small Interfering
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Cyclin D1
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Proto-Oncogene Proteins c-akt
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CDK2 protein, human
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CDK4 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Calcium
Grants and funding
This study was supported by the Region Picardie, and by the Ministère de l'Education Nationale (France). The funders had no role in study design, data collection and analysis, in the decision to publish, or in preparation of the manuscript.