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 journalArticlepeer-review

14 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

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)

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