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

Ji Hee Kim; Sayamaa Lkhagvadorj; Mi Ra Lee; Kyu Hee Hwang; Hyun Chul Chung; Jae Hung Jung; Seung Kuy Cha; Minseob Eom

doi:10.1016/j.bbrc.2014.04.064

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

Ji Hee Kim, Sayamaa Lkhagvadorj, Mi Ra Lee, Kyu Hee Hwang, Hyun Chul Chung, Jae Hung Jung, Seung Kuy Cha, Minseob Eom

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	76-82
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	448
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2014.04.064
Publication status	Published - 2014 May 23

Bibliographical note

Funding 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

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2014.04.064

Cite this

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title = "Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma",

abstract = "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.",

author = "Kim, {Ji Hee} and Sayamaa Lkhagvadorj and Lee, {Mi Ra} and Hwang, {Kyu Hee} and Chung, {Hyun Chul} and Jung, {Jae Hung} and Cha, {Seung Kuy} and Minseob Eom",

note = "Funding 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.).",

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AU - Kim, Ji Hee

AU - Lkhagvadorj, Sayamaa

AU - Lee, Mi Ra

AU - Hwang, Kyu Hee

AU - Chung, Hyun Chul

AU - Jung, Jae Hung

AU - Cha, Seung Kuy

AU - Eom, Minseob

N1 - Funding 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.).

PY - 2014/5/23

Y1 - 2014/5/23

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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