Physiological functions of calcium signaling via Orai1 in cancer
Intracellular calcium (Ca ) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca entry (SOCE) is a major mechanism by which Ca is imported from the extracellular space to the intracellular space, especially...
Saved in:
Published in | The journal of physiological sciences Vol. 73; no. 1; p. 21 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Japan
Springer
27.09.2023
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Intracellular calcium (Ca
) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca
entry (SOCE) is a major mechanism by which Ca
is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca
entry (SOCE) is also a receptor-regulated Ca
entry pathway that maintains Ca
homeostasis by sensing reduced Ca
levels in the endoplasmic reticulum (ER). In general, the activation of G protein-coupled receptors (GPCRs) or immunoreceptors, such as T-cell, B-cell and Fc receptors, results in the production of inositol 1,4,5-trisphosphate (IP
). IP
binds to IP
receptors located in the ER membrane. The, IP
receptors in the ER membrane trigger a rapid and transient release of Ca
from the ER store. The resulting depletion of ER Ca
concentrations is sensed by the EF-hand motif of stromal interaction molecule (STIM), i.e., calcium sensor, which then translocates to the plasma membrane (PM). STIM interacts with Orai Ca
channel subunits (also known as CRACM1) on the PM, leading to Ca
influx from the extracellular space to increase intracellular Ca
concentrations. The physiological functions of Orai and STIM have been studied mainly with respect to their roles in the immune system. Based on numerous previous studies, Orai channels (Orai1, Orai2 and Orai3 channels) control Ca
release-activated Ca
(CRAC) currents and contribute to SOCE currents in other types of cells, including various cancer cells. There are many reports that Orai1 is involved in cell proliferation, migration, metastasis, apoptosis and epithelial-mesenchymal transition (EMT) in various cancers. We previously found that Orai1 plays important roles in cell apoptosis and migration in melanoma. Recently, we reported novel evidence of Orai1 in human oral squamous cell carcinoma (OSCC) cells and human cardiac fibroblasts (HCFs). In this review, we present multiple physiological functions of Orai1 in various cancer cells and cardiac fibroblasts, including our findings. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 1880-6562 1880-6546 1880-6562 |
DOI: | 10.1186/s12576-023-00878-0 |