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Updated: May 14, 2026

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
The ER Ca²⁺ sensor STIM1 regulates actomyosin contractility of migratory cells
Ying-Ting Chen1, Yih-Fung Chen, Wen-Tai Chiu
1Department of Biomedical Engineering, College of Egineering, National Cheng Kung University, Tainan 701, Taiwan.
Abstract:
Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum (ER) Ca(2+) sensor that triggers the store-operated Ca(2+) entry (SOCE). The clinical relevance of STIM1 has been highlighted in breast and cervical cancer, but the molecular mechanism by which STIM1 promotes cancer progression remains unclear. This study explores the regulatory mechanisms by which STIM1-dependent Ca(2+) signaling controls cancer cell migration. Three different SOCE inhibitors, SKF96365, 2-APB and YM-58483, significantly inhibited cervical cancer cell migration to a similar extent to that of STIM1 silencing. In contrast, STIM1 overexpression significantly enhanced cervical cancer cell migration. Live cell confocal images and three-dimensional tomograms showed that STIM1 formed aggregates and translocated towards the plasma membranes of migratory cells, and this was accompanied by increasing cytosolic Ca(2+) spikes. STIM1 silencing also inhibited the recruitment and association of active focal adhesion kinase (pTyr397-FAK) and talin at focal adhesions, indicating the blockade of force transduction from integrin signaling. Epidermal growth factor-induced phosphorylation of myosin II regulatory light chains was abolished by STIM1 knockdown and SOCE inhibition. Dual immunostaining of activated myosin II (pSer19-MLC) and actin revealed that actomyosin formation depended on STIM1-mediated Ca(2+) entry. Most importantly, STIM1 expression levels as well as SOCE activity controlled the generation of cell contractile force, as measured by the microfabricated post-array-detector system. These results highlight the unique role of STIM1-dependent Ca(2+) signaling in controlling cell migration by the regulation of actomyosin reorganization in conjunction with enhanced contractile forces.
Insights
Stromal interaction molecule 1 (STIM1) regulates cancer cell migration by controlling calcium signaling and actomyosin contractility. STIM1
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensor crucial for store-operated calcium entry (SOCE).
- STIM1's role in cancer progression, particularly in breast and cervical cancers, is recognized, but its precise molecular mechanisms driving migration are not fully understood.
Purpose of the Study:
- To investigate the regulatory mechanisms by which STIM1-dependent calcium signaling influences cancer cell migration.
- To elucidate the role of STIM1 in focal adhesion dynamics, actomyosin organization, and cell contractile force generation.
Main Methods:
- Utilized SOCE inhibitors (SKF96365, 2-APB, YM-58483) and STIM1 silencing/overexpression in cervical cancer cells.
- Employed live cell confocal microscopy and 3D tomograms to visualize STIM1 localization and dynamics.
- Assessed focal adhesion kinase (FAK) and talin recruitment, myosin II phosphorylation, actomyosin formation, and cell contractile force using a post-array-detector system.
Main Results:
- SOCE inhibitors and STIM1 silencing significantly reduced cervical cancer cell migration, while STIM1 overexpression enhanced it.
- STIM1 translocation to the plasma membrane correlated with increased cytosolic calcium spikes and was essential for focal adhesion dynamics.
- STIM1 is critical for epidermal growth factor-induced myosin II phosphorylation, actomyosin formation, and the generation of cell contractile force.
Conclusions:
- STIM1-dependent calcium signaling plays a pivotal role in regulating cancer cell migration.
- STIM1 controls cell migration through the modulation of actomyosin reorganization and the enhancement of cellular contractile forces.
- These findings highlight STIM1 as a potential therapeutic target for inhibiting cancer progression.
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