title: Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma.
abstract: 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.
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Sayamaa
authors.initials: S
authors.lastname: Lkhagvadorj
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Mi-Ra
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Kyu-Hee
authors.initials: KH
authors.lastname: Hwang
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Jae Hung
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: skcha@yonsei.ac.kr.
authors.forename: Seung-Kuy
authors.initials: SK
authors.lastname: Cha
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: eomm@yonsei.ac.kr.
authors.forename: Minseob
authors.initials: M
authors.lastname: Eom
mesh_terms: D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1
keywords: Clear cell renal cell carcinoma; Migration; Orai1; Proliferation; STIM1; Store-operated Ca(2+) channel