Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Biochem Biophys Res Commun. 2014 May 23;448(1):76-82. doi: 10.1016/j.bbrc.2014.04.064. Epub 2014 Apr 19.
The intracellular Ca(2+) regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca(2+) entry (SOCE) is a major Ca(2+) entry mechanism in non-excitable cells, being involved in cell proliferation and migration in several types of cancer. However, the expression and biological role of SOCE have not been investigated in clear cell renal cell carcinoma (ccRCC). Here, we demonstrate that Orai1 and STIM1, not Orai3, are crucial components of SOCE in the progression of ccRCC. The expression levels of Orai1 in tumor tissues were significantly higher than those in the adjacent normal parenchymal tissues. In addition, native SOCE was blunted by inhibiting SOCE or by silencing Orai1 and STIM1. Pharmacological blockade or knockdown of Orai1 or STIM1 also significantly inhibited RCC cell migration and proliferative capability. Taken together, Orai1 is highly expressed in ccRCC tissues illuminating that Orai1-mediated SOCE may play an important role in ccRCC development. Indeed, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration.
细胞内 Ca(2+) 调节与肿瘤发生和肿瘤进展有关。值得注意的是，储存操作的 Ca(2+) 内流 (SOCE) 是非兴奋细胞中的主要 Ca(2+) 内流机制，涉及多种类型癌症中的细胞增殖和迁移。然而，SOCE 的表达和生物学作用在透明细胞肾细胞癌 (ccRCC) 中尚未得到研究。在这里，我们证明 Orai1 和 STIM1（而不是 Orai3）是 ccRCC 进展中 SOCE 的关键组成部分。肿瘤组织中 Orai1 的表达水平明显高于相邻正常实质组织。此外，通过抑制 SOCE 或沉默 Orai1 和 STIM1 ，可使内源性 SOCE 减弱。Orai1 或 STIM1 的药理学阻断或敲低也显著抑制了 RCC 细胞的迁移和增殖能力。总之，Orai1 在 ccRCC 组织中高度表达，表明 Orai1 介导的 SOCE 可能在 ccRCC 发展中发挥重要作用。事实上，Orai1 和 STIM1 通过促进细胞增殖和迁移构成了 ccRCC 中的天然 SOCE 途径。
