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Role of Orai3 in the Pathophysiology of Cancer

Jose Sanchez-Collado1, Isaac Jardin1, Jose J López1

  • 1Cell Physiology Research Group, Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain.

International Journal of Molecular Sciences
|November 13, 2021
PubMed

Insights

The Orai3 calcium channel is overexpressed in cancer, influencing cell growth and survival. This review details Orai3

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The Orai3 channel is a mammalian-exclusive calcium channel involved in two distinct calcium currents: store-operated current (Icrac) and store-independent arachidonic acid (AA)-regulated current (Iarc).
  • Orai3 interacts with stromal interaction molecules (STIM) and other Orai proteins (Orai1/Orai2) in calcium influx pathways.
  • Orai3 overexpression is observed in various cancer cells and tissues compared to normal counterparts.

Purpose of the Study:

  • To review the current understanding of Orai3's functional role in cancer pathogenesis.
  • To explore the cell-specific relevance of Orai3 in calcium influx across different cancer types.
  • To summarize Orai3's contribution to cancer hallmarks such as proliferation and apoptosis resistance.

Main Methods:

  • Literature review of existing studies on Orai3 function in cancer.
  • Analysis of Orai3 expression patterns in neoplastic versus non-tumor cells.
  • Examination of Orai3's role in specific calcium entry pathways (SOCE, AA-regulated) in various cancers.

Main Results:

  • Orai3's role in store-operated calcium entry (SOCE) is cell-specific: crucial in estrogen receptor-positive breast cancer and non-small cell lung cancer (NSCLC), and modulatory in colorectal and pancreatic cancers.
  • In prostate cancer, Orai3 forms heteromeric channels with Orai1, regulated by AA, reducing SOCE and promoting proliferation.
  • Orai3 overexpression supports key cancer hallmarks including cell cycle progression, proliferation, migration, and resistance to apoptosis.

Conclusions:

  • Orai3 plays a significant, albeit cell-specific, role in the pathogenesis of various cancers.
  • Targeting Orai3 may offer a therapeutic strategy for cancers where it drives proliferation and survival.
  • Further research into Orai3's precise mechanisms in different cancer types is warranted.
Keywords:
calcium entrycancerorai1orai3

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