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

Abstract

BackgroundIn 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 Ca2+ 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).ResultsEGF 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.ConclusionsOur 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.

Involvement of L‐type Ca2+ channel and toll‐like receptor‐4 in nickel‐induced interleukin‐8 gene expression

“…Considering the concept of metal ion mimicry, calcium channels are very likely to be transducers of nickel. Indeed, calcium channels have been considered as important mediators of inflammatory gene activation Wang et al, 2012;Yang et al, 2013;Guo et al, 2013). In addition, pretreatment with the calcium channel blockers, verapamil and nicardipine, decreased nickel uptake by 20% (Funakoshi et al, 1997).…”

Roles of store-operated Ca2+channels in regulating cell cycling and migration of human cardiac c-kit+progenitor cells

“…Ca 2ϩ signaling through SOCE channels generates cellular Ca 2ϩ elevations and activates downstream molecular signaling by coupling to the related enzymes and transcription factors that regulate many functions, including gene expression, exocytosis, and cell proliferation and migration (12,24,52). Silencing SOCE components STIM1 and/or Orai1 signif- icantly attenuates cell proliferation in mouse embryonic and adult mouse neural stem/progenitor cells (1), mouse airway smooth muscle cells (46), rat vascular smooth muscle cells (20), and human retinal pigment epithelial cells (55). In addition, silencing TRPC1 inhibited the proliferation of canine kidney cells (33).…”

Tectonic 1 accelerates gastric cancer cell proliferation and cell cycle progression in vitro

“…Also, TCTN1 could have other functions in addition to regulating the Hh pathway. Recently, calcium signaling particularly Orai1/Ca 2+ release-activated Ca 2+ channel M1 has been shown to be the most important regulatory signal in cell cycle arrest as well as cancer cell proliferation (30,31). Whether TCTN1 induced G 2 /M phase cell cycle arrest due to regulation of calcium signaling in gastric cancer remains to be investigated.…”