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Updated: Sep 13, 2025

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model
Published on: June 11, 2014
STIM-IP3R crosstalk regulates migration of breast cancer cells
Ruslana Militsin1, Hadas Achildiev Cohen1, Maya Hershfinkel1
1Department of Biochemistry, Technion Integrated Cancer Center, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Abstract:
Calcium ions (Ca2+) are crucial second messengers involved in numerous processes including tumorigenesis and cancer cell migration. Previous studies have shown that the endoplasmic reticulum (ER) Ca2+ sensors, stromal interaction molecules STIM1 and STIM2, are key regulators of cancer cell migration. In this study, using breast cancer cells lacking one or both STIM isoforms we show that although STIM proteins are critical regulators of cell migration, they are dispensable for this cellular activity. The mechanism underlying this complex effect involves functional crosstalk between STIM proteins and inositol 1,4,5-trisphosphate receptors (IP3Rs). Our findings indicate that beyond their classical role in store-operated Ca2+ entry, STIM proteins shape the spatial dynamics of IP3R-mediated Ca2+ release. Our results suggest that following ER Ca2+ depletion, the activated STIM proteins shift the pattern of IP3R-mediated Ca2+ release from a localized signal, which promotes cell migration, to a more diffuse signal, which attenuates cell migration.
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