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When huffing and puffing Ca2+ goes global, breast cancer cells are unmoved

Woo Young Chung1, Shmuel Muallem1

  • 1Epithelial Signaling and Transport Section, National Institute of Dental Craniofacial Research, National Institutes of Health , Bethesda, MD, USA.

The Journal of Cell Biology
|August 19, 2025
PubMed

Insights

Stromal interaction molecules (STIM)1 and STIM2 regulate calcium dynamics beyond their known functions. This study reveals their novel role in controlling breast cancer cell migration and invasion.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Stromal interaction molecules (STIM)1 and STIM2 are known endoplasmic reticulum (ER) calcium sensors that activate Orai1 channels.
  • Their role in regulating calcium (Ca2+) dynamics in cancer progression is not fully understood.

Purpose of the Study:

  • To investigate the non-canonical functions of STIM1 and STIM2 in breast cancer.
  • To elucidate the role of STIM1 and STIM2 in regulating inositol trisphosphate receptor (IP3R)-mediated Ca2+ dynamics.
  • To determine the impact of these Ca2+ signaling pathways on breast cancer cell migration and invasion.

Main Methods:

  • CRISPR-Cas9 gene editing to generate STIM1 and STIM2 knockout cell lines.
  • Confocal microscopy to visualize Ca2+ dynamics.
  • Live-cell imaging to assess cell migration and invasion.
  • Biochemical assays to analyze protein interactions.

Main Results:

  • STIM1 and STIM2 regulate IP3R-mediated Ca2+ release from the ER.
  • Disruption of STIM1 and STIM2 function impairs breast cancer cell migration and invasion.
  • STIM1 and STIM2 directly influence Ca2+ signaling pathways critical for cancer cell motility.

Conclusions:

  • STIM1 and STIM2 possess functions beyond ER Ca2+ sensing and Orai1 activation.
  • These proteins are critical regulators of breast cancer cell migration and invasion through modulation of IP3R-mediated Ca2+ signaling.
  • Targeting STIM1 and STIM2 may offer novel therapeutic strategies for breast cancer treatment.

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