Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

被引：89

作者：

Kim, Ji-Hee ^{[1
]}

Lkhagvadorj, Sayamaa ^{[2
]}

Lee, Mi-Ra ^{[2
]}

Hwang, Kyu-Hee ^{[1
]}

Chung, Hyun Chul ^{[3
]}

Jung, Jae Hung ^{[3
]}

Cha, Seung-Kuy ^{[1
,4
,5
]}

Eom, Minseob ^{[2
]}

机构：

[1] Yonsei Univ, Wonju Coll Med, Dept Physiol, Wonju 220701, Gangwondo, South Korea

[2] Yonsei Univ, Wonju Coll Med, Dept Pathol, Wonju 220701, Gangwondo, South Korea

[3] Yonsei Univ, Wonju Coll Med, Dept Urol, Wonju 220701, Gangwondo, South Korea

[4] Yonsei Univ, Wonju Coll Med, Inst Lifestyle Med, Wonju 220701, Gangwondo, South Korea

[5] Yonsei Univ, Wonju Coll Med, Nucl Receptor Res Consortium, Wonju 220701, Gangwondo, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 448卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Orai1; STIM1; Store-operated Ca2+ channel; Clear cell renal cell carcinoma; Migration; Proliferation; CANCER CELLS; CALCIUM; CA2+; CHANNELS; DISEASE; METASTASIS; ACTIVATION; INVASION; PATHWAY;

D O I：

10.1016/j.bbrc.2014.04.064

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The intracellular Ca2+ regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca2+ entry (SOCE) is a major Ca2+ 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, rail and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：76 / 82

页数：7

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