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
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DOI：
10.1016/j.bbamcr.2012.12.009
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发表时间：
2013-03-01
影响因子：
5.1
通讯作者：
Ouadid-Ahidouch, Halima
中科院分区：
文献类型：
--
作者：
Faouzi, Malika;Kischel, Philippe;Ouadid-Ahidouch, Halima
Orai家族的成员是高度选择性的钙离子通道，在储存操作的钙进入中起重要作用。在已知的三种Orai亚型中，Orai3因其在癌症中的新作用而受到越来越多的关注。我们最近证明Orai3通道在乳腺癌（BC）活检中过度表达，并特异性地参与MCF-7 BC细胞的增殖、细胞周期进展和存活。在这里，我们研究了受Orai3沉默影响的下游信号机制，导致MCF-7癌细胞特异性的后续功能影响。我们报告了肿瘤组织和MCF-7癌细胞系中Orai3和c-myc表达之间的相关性，证明Orai3下调可降低原癌基因c-myc的表达和活性。这可能是通过MAP激酶途径介导的，因为我们观察到Orai3沉默后，pERK1/2水平降低，细胞周期阻滞在G1期。我们的研究结果提供了强有力的证据，证明c-myc原癌基因通过MAP激酶途径受到储存操作的钙进入通道Orai3的影响。这一联系为Orai3通道与MCF-7 BC细胞增殖、细胞周期进展和存活的下游机制提供了新的线索。(c) 2012 Elsevier B.V.版权所有
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. (c) 2012 Elsevier B.V. All rights reserved.