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, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2014 May 23|
Bibliographical noteFunding Information:
We thank Minseon Kim at Yonsei University Wonju College of Medicine for critical reading and comments on the manuscript. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning ( NRF-2012R1A1A1004233 to M.E.) and the Ministry of Education ( NRF-2010-0024789 to S.-K.C.) and a research grant from Yonsei University Wonju College of Medicine ( YUWCM-2013-19 to S.-K.C.).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology