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.

Journal of Cell Science
|February 5, 2013
PubMed

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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