TY - JOUR
T1 - Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells
AU - Yang, I. Hui
AU - Tsai, Yao Ting
AU - Chiu, Siou Jin
AU - Liu, Li Teh
AU - Lee, Hsuan Hung
AU - Hou, Ming Feng
AU - Hsu, Wen Li
AU - Chen, Ben Kuen
AU - Chang, Wei Chiao
N1 - Funding Information:
We thank to the experimental help from Yih-Chi Hu and Wei-Chiao Chen. This study was supported by Chang Gung Medical Research Program Grant (CMRPG8A0131) and by fundings from an Excellence for Cancer Research Center grant, Department of Health, Executive Yuan, Taiwan, R.O.C. (DOH102-TD-C-111-002) and grants from National Science Council (NSC101-2628-B038-001-MY2; NSC101-2320-B038-029-MY3).
PY - 2013
Y1 - 2013
N2 - Background: In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca§ssup§ 2+§esup§ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line). Results: EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation. Conclusions: Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders.
AB - Background: In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca§ssup§ 2+§esup§ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line). Results: EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation. Conclusions: Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders.
KW - Orai1
KW - Proliferative vitreoretinopathy
KW - Retinal pigment epithelial cell
KW - STIM1
KW - Store-operated calcium channel
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U2 - 10.1186/1423-0127-20-41
DO - 10.1186/1423-0127-20-41
M3 - Article
C2 - 23800047
AN - SCOPUS:84879235324
SN - 1021-7770
VL - 20
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
IS - 1
M1 - 41
ER -