Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells

Ming Feng Hou; Ho Chang Kuo; Jih Heng Li; Yu Shiuan Wang; Chen Chia Chang; Ku Chung Chen; Wei Chiao Chen; Chien Chih Chiu; Shengyu Yang; Wei Chiao Chang

doi:10.1016/j.bbagen.2011.07.001

Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells

Ming Feng Hou, Ho Chang Kuo, Jih Heng Li, Yu Shiuan Wang, Chen Chia Chang, Ku Chung Chen, Wei Chiao Chen, Chien Chih Chiu, Shengyu Yang, Wei Chiao Chang

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

57 Citations (Scopus)

Abstract

Background: Orai1/CRACM1 is a principal component of the store-operated calcium channels. Store-operated calcium influx is highly correlated with inflammatory reactions, immunological regulation, and cell proliferation. Epidermal growth factor (EGF), which plays an important role in the regulation of cell proliferation, can activate store-operated calcium channels. However, the consequences of Orai1/CRACM1 overexpression in EGF-mediated lung cancer cells growth are not known. Methods: To investigate the role of Orai1/CRACM1 in EGF-mediated lung cancer cell proliferation, Orai1/CRACM1 plasmids were transfected into cells by lipofection. A cell proliferation assay, immunofluorescence staining, flow cytometry, and real-time polymerase chain reaction were employed to monitor cell proliferation. The calcium influx signals were investigated using a fluorescent-based calcium assay. Results: Transfection of Orai1/CRACM1 plasmids resulted in the inhibition of EGF-mediated cell proliferation. ERK1/2 and Akt phosphorylation were inhibited by Orai1/CRACM1 overexpression. Expression of the cell cycle modulator p21 was induced in the Orai1/CRACM1-overexpressing cells, whereas the expression of cyclin D3 was reduced. Flow cytometry revealed that overexpression of Orai1/CRACM1 resulted in G0/G1 cell cycle arrest. Importantly, Orai1/CRACM1 overexpression significantly attenuated EGF-mediated store-operated calcium influx. In addition, application of 2-APB, a store-operated calcium channel inhibitor, resulted in the inhibition of EGF-mediated cancer cell proliferation. Conclusions: We conclude that Orai1/CRACM1 overexpression attenuates store-operated Ca ²⁺ influx that in turn blocks EGF-mediated proliferative signaling and drives cell cycle arrest.

Original language	English
Pages (from-to)	1278-1284
Number of pages	7
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1810
Issue number	12
DOIs	https://doi.org/10.1016/j.bbagen.2011.07.001
Publication status	Published - Dec 2011

Keywords

Cell proliferation
Lung cancer
Orai1/CRACM1
p21

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

UN SDGs

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

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10.1016/j.bbagen.2011.07.001

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Hou, M. F., Kuo, H. C., Li, J. H., Wang, Y. S., Chang, C. C., Chen, K. C., Chen, W. C., Chiu, C. C., Yang, S., & Chang, W. C. (2011). Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells. Biochimica et Biophysica Acta - General Subjects, 1810(12), 1278-1284. https://doi.org/10.1016/j.bbagen.2011.07.001

Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells. / Hou, Ming Feng; Kuo, Ho Chang; Li, Jih Heng et al.
In: Biochimica et Biophysica Acta - General Subjects, Vol. 1810, No. 12, 12.2011, p. 1278-1284.

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

Hou, MF, Kuo, HC, Li, JH, Wang, YS, Chang, CC, Chen, KC, Chen, WC, Chiu, CC, Yang, S & Chang, WC 2011, 'Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells', Biochimica et Biophysica Acta - General Subjects, vol. 1810, no. 12, pp. 1278-1284. https://doi.org/10.1016/j.bbagen.2011.07.001

@article{48e4c625e714495287f6b8729dc1a100,

title = "Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells",

abstract = "Background: Orai1/CRACM1 is a principal component of the store-operated calcium channels. Store-operated calcium influx is highly correlated with inflammatory reactions, immunological regulation, and cell proliferation. Epidermal growth factor (EGF), which plays an important role in the regulation of cell proliferation, can activate store-operated calcium channels. However, the consequences of Orai1/CRACM1 overexpression in EGF-mediated lung cancer cells growth are not known. Methods: To investigate the role of Orai1/CRACM1 in EGF-mediated lung cancer cell proliferation, Orai1/CRACM1 plasmids were transfected into cells by lipofection. A cell proliferation assay, immunofluorescence staining, flow cytometry, and real-time polymerase chain reaction were employed to monitor cell proliferation. The calcium influx signals were investigated using a fluorescent-based calcium assay. Results: Transfection of Orai1/CRACM1 plasmids resulted in the inhibition of EGF-mediated cell proliferation. ERK1/2 and Akt phosphorylation were inhibited by Orai1/CRACM1 overexpression. Expression of the cell cycle modulator p21 was induced in the Orai1/CRACM1-overexpressing cells, whereas the expression of cyclin D3 was reduced. Flow cytometry revealed that overexpression of Orai1/CRACM1 resulted in G0/G1 cell cycle arrest. Importantly, Orai1/CRACM1 overexpression significantly attenuated EGF-mediated store-operated calcium influx. In addition, application of 2-APB, a store-operated calcium channel inhibitor, resulted in the inhibition of EGF-mediated cancer cell proliferation. Conclusions: We conclude that Orai1/CRACM1 overexpression attenuates store-operated Ca 2+ influx that in turn blocks EGF-mediated proliferative signaling and drives cell cycle arrest.",

keywords = "Cell proliferation, Lung cancer, Orai1/CRACM1, p21",

author = "Hou, {Ming Feng} and Kuo, {Ho Chang} and Li, {Jih Heng} and Wang, {Yu Shiuan} and Chang, {Chen Chia} and Chen, {Ku Chung} and Chen, {Wei Chiao} and Chiu, {Chien Chih} and Shengyu Yang and Chang, {Wei Chiao}",

note = "Funding Information: This work is supported by the following grants: Excellence for cancer research center grant , Department of Health, Executive Yuan, Taiwan, ROC (no. DOH100-TD-C-111-002 ) and National Science Council , Taiwan, ROC (NSC 100-2320-B-037-002 ) to W.C. Chang.",

year = "2011",

month = dec,

doi = "10.1016/j.bbagen.2011.07.001",

language = "English",

volume = "1810",

pages = "1278--1284",

journal = "Biochimica et Biophysica Acta - General Subjects",

issn = "0304-4165",

publisher = "Elsevier B.V.",

number = "12",

}

TY - JOUR

T1 - Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells

AU - Hou, Ming Feng

AU - Kuo, Ho Chang

AU - Li, Jih Heng

AU - Wang, Yu Shiuan

AU - Chang, Chen Chia

AU - Chen, Ku Chung

AU - Chen, Wei Chiao

AU - Chiu, Chien Chih

AU - Yang, Shengyu

AU - Chang, Wei Chiao

N1 - Funding Information: This work is supported by the following grants: Excellence for cancer research center grant , Department of Health, Executive Yuan, Taiwan, ROC (no. DOH100-TD-C-111-002 ) and National Science Council , Taiwan, ROC (NSC 100-2320-B-037-002 ) to W.C. Chang.

PY - 2011/12

Y1 - 2011/12

N2 - Background: Orai1/CRACM1 is a principal component of the store-operated calcium channels. Store-operated calcium influx is highly correlated with inflammatory reactions, immunological regulation, and cell proliferation. Epidermal growth factor (EGF), which plays an important role in the regulation of cell proliferation, can activate store-operated calcium channels. However, the consequences of Orai1/CRACM1 overexpression in EGF-mediated lung cancer cells growth are not known. Methods: To investigate the role of Orai1/CRACM1 in EGF-mediated lung cancer cell proliferation, Orai1/CRACM1 plasmids were transfected into cells by lipofection. A cell proliferation assay, immunofluorescence staining, flow cytometry, and real-time polymerase chain reaction were employed to monitor cell proliferation. The calcium influx signals were investigated using a fluorescent-based calcium assay. Results: Transfection of Orai1/CRACM1 plasmids resulted in the inhibition of EGF-mediated cell proliferation. ERK1/2 and Akt phosphorylation were inhibited by Orai1/CRACM1 overexpression. Expression of the cell cycle modulator p21 was induced in the Orai1/CRACM1-overexpressing cells, whereas the expression of cyclin D3 was reduced. Flow cytometry revealed that overexpression of Orai1/CRACM1 resulted in G0/G1 cell cycle arrest. Importantly, Orai1/CRACM1 overexpression significantly attenuated EGF-mediated store-operated calcium influx. In addition, application of 2-APB, a store-operated calcium channel inhibitor, resulted in the inhibition of EGF-mediated cancer cell proliferation. Conclusions: We conclude that Orai1/CRACM1 overexpression attenuates store-operated Ca 2+ influx that in turn blocks EGF-mediated proliferative signaling and drives cell cycle arrest.

AB - Background: Orai1/CRACM1 is a principal component of the store-operated calcium channels. Store-operated calcium influx is highly correlated with inflammatory reactions, immunological regulation, and cell proliferation. Epidermal growth factor (EGF), which plays an important role in the regulation of cell proliferation, can activate store-operated calcium channels. However, the consequences of Orai1/CRACM1 overexpression in EGF-mediated lung cancer cells growth are not known. Methods: To investigate the role of Orai1/CRACM1 in EGF-mediated lung cancer cell proliferation, Orai1/CRACM1 plasmids were transfected into cells by lipofection. A cell proliferation assay, immunofluorescence staining, flow cytometry, and real-time polymerase chain reaction were employed to monitor cell proliferation. The calcium influx signals were investigated using a fluorescent-based calcium assay. Results: Transfection of Orai1/CRACM1 plasmids resulted in the inhibition of EGF-mediated cell proliferation. ERK1/2 and Akt phosphorylation were inhibited by Orai1/CRACM1 overexpression. Expression of the cell cycle modulator p21 was induced in the Orai1/CRACM1-overexpressing cells, whereas the expression of cyclin D3 was reduced. Flow cytometry revealed that overexpression of Orai1/CRACM1 resulted in G0/G1 cell cycle arrest. Importantly, Orai1/CRACM1 overexpression significantly attenuated EGF-mediated store-operated calcium influx. In addition, application of 2-APB, a store-operated calcium channel inhibitor, resulted in the inhibition of EGF-mediated cancer cell proliferation. Conclusions: We conclude that Orai1/CRACM1 overexpression attenuates store-operated Ca 2+ influx that in turn blocks EGF-mediated proliferative signaling and drives cell cycle arrest.

KW - Cell proliferation

KW - Lung cancer

KW - Orai1/CRACM1

KW - p21

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Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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