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

Highlights: • Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. • Orai1 and STIM1 constitute a native store-operated Ca{sup 2+} entry in ccRCC cells. • Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. - Abstract: The intracellular Ca{sup 2+} regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca{sup 2+} entry (SOCE) is a major Ca{sup 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 amore » native SOCE pathway in ccRCC by promoting cell proliferation and migration.« less
Authors:
 [1] ; ;  [2] ;  [1] ; ;  [3] ;  [1] ;  [4] ;  [2]
  1. Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
  2. Department of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
  3. Department of Urology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
  4. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416438
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 448; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CALCIUM IONS; CARCINOMAS; CELL PROLIFERATION; KIDNEYS; MIGRATION; PHARMACOLOGY; TUMOR CELLS