Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells

I. Hui Yang, Yao Ting Tsai, Siou Jin Chiu, Li Teh Liu, Hsuan Hung Lee, Ming Feng Hou, Wen Li Hsu, Ben Kuen Chen, Wei Chiao Chang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number41
JournalJournal of Biomedical Science
Volume20
Issue number1
DOIs
Publication statusPublished - 2013

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Retinal Pigments
Cell proliferation
Cell growth
Epidermal Growth Factor
Cell Movement
Calcium Channels
Epithelial Cells
Cell Proliferation
Mitogen-Activated Protein Kinase Kinases
Growth
Phosphorylation
Phosphatidylinositol 3-Kinases
Phosphatidylinositol 3-Kinase
Extracellular Signal-Regulated MAP Kinases
Cell membranes
Protein Kinases
Small Interfering RNA
Cells
Cell Membrane
Pharmacology

Keywords

  • Orai1
  • Proliferative vitreoretinopathy
  • Retinal pigment epithelial cell
  • STIM1
  • Store-operated calcium channel

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells. / Yang, I. Hui; Tsai, Yao Ting; Chiu, Siou Jin; Liu, Li Teh; Lee, Hsuan Hung; Hou, Ming Feng; Hsu, Wen Li; Chen, Ben Kuen; Chang, Wei Chiao.

In: Journal of Biomedical Science, Vol. 20, No. 1, 41, 2013.

Research output: Contribution to journalArticle

Yang, I. Hui ; Tsai, Yao Ting ; Chiu, Siou Jin ; Liu, Li Teh ; Lee, Hsuan Hung ; Hou, Ming Feng ; Hsu, Wen Li ; Chen, Ben Kuen ; Chang, Wei Chiao. / Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells. In: Journal of Biomedical Science. 2013 ; Vol. 20, No. 1.
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abstract = "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.",
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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

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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.

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KW - Proliferative vitreoretinopathy

KW - Retinal pigment epithelial cell

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KW - Store-operated calcium channel

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