+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

ORAI3 silencing alters cell proliferation and cell cycle progression via c-myc pathway in breast cancer cells



ORAI3 silencing alters cell proliferation and cell cycle progression via c-myc pathway in breast cancer cells



Biochimica et Biophysica Acta 1833(3): 752-760



Members of the Orai family are highly selective calcium ion channels that play an important role in store-operated calcium entry. Among the three known Orai isoforms, Orai3 has gained increased attention, notably for its emerging role in cancer. We recently demonstrated that Orai3 channels are over-expressed in breast cancer (BC) biopsies, and involved specifically in proliferation, cell cycle progression and survival of MCF-7 BC cells. Here, we investigate the downstream signaling mechanisms affected by Orai3 silencing, leading to the subsequent functional impact specifically seen in MCF-7 cancer cells. We report a correlation between Orai3 and c-myc expression in tumor tissues and in the MCF-7 cancer cell line by demonstrating that Orai3 down-regulation reduces both expression and activity of the proto-oncogene c-myc. This is likely mediated through the MAP Kinase pathway, as we observed decreased pERK1/2 levels and cell-cycle arrest in G1 phase after Orai3 silencing. Our results provide strong evidence that the c-myc proto-oncogene is influenced by the store-operated calcium entry channel Orai3 through the MAP kinase pathway. This connection provides new clues in the downstream mechanism linking Orai3 channels and proliferation, cell cycle progression and survival of MCF-7 BC cells.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036717953

Download citation: RISBibTeXText

PMID: 23266555

DOI: 10.1016/j.bbamcr.2012.12.009


Related references

Down-regulation of Orai3 arrests cell-cycle progression and induces apoptosis in breast cancer cells but not in normal breast epithelial cells. Journal of Cellular Physiology 226(2): 542-551, 2011

Bisphenol S promotes the cell cycle progression and cell proliferation through ERα-cyclin D-CDK4/6-pRb pathway in MCF-7 breast cancer cells. Toxicology and Applied Pharmacology 366: 75-82, 2019

RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells. Cancer Letters 321(1): 80-88, 2012

Lentivirus-Mediated Silencing of Myosin VI Inhibits Proliferation and Cell Cycle Progression in Human Lung Cancer Cells. Chemical Biology and Drug Design 86(4): 606-613, 2015

Silencing the Metallothionein-2A gene inhibits cell cycle progression from G1- to S-phase involving ATM and cdc25A signaling in breast cancer cells. Cancer Letters 276(1): 109-117, 2008

Extracellular matrix collagen alters cell proliferation and cell cycle progression of human uterine leiomyoma smooth muscle cells. Plos one 8(9): E75844, 2013

IARS2 silencing induces non-small cell lung cancer cells proliferation inhibition, cell cycle arrest and promotes cell apoptosis. Neoplasma 63(1): 64-71, 2016

The effects of cyclooxygenase-2 gene silencing by siRNA on cell proliferation, cell apoptosis, cell cycle and tumorigenicity of Capan-2 human pancreatic cancer cells. Oncology Reports 27(4): 1003-1010, 2012

ADAM17 regulates prostate cancer cell proliferation through mediating cell cycle progression by EGFR/PI3K/AKT pathway. Molecular and Cellular Biochemistry 359(1-2): 235-243, 2012

RNA interference-mediated silencing of NANOG leads to reduced proliferation and self-renewal, cell cycle arrest and apoptosis in T-cell acute lymphoblastic leukemia cells via the p53 signaling pathway. Leukemia Research 37(9): 1170-1177, 2013

Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation. Oncology Reports 21(6): 1525-1528, 2009

KIAA0101 inhibition suppresses cell proliferation and cell cycle progression by promoting the interaction between p53 and Sp1 in breast cancer. Biochemical and Biophysical Research Communications 503(2): 600-606, 2018

PSMD2 regulates breast cancer cell proliferation and cell cycle progression by modulating p21 and p27 proteasomal degradation. Cancer Letters 430: 109-122, 2018

The novel long non‑coding RNA PRNCR1‑2 is involved in breast cancer cell proliferation, migration, invasion and cell cycle progression. Molecular Medicine Reports 19(3): 1824-1832, 2019

Chalcone inhibits the proliferation of human breast cancer cell by blocking cell cycle progression and inducing apoptosis. Food and Chemical Toxicology 44(5): 704-713, 2006