Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Cell Sci. 2013 Mar 1;126(Pt 5):1260-7. doi: 10.1242/jcs.121129. Epub 2013 Feb 1.

The ER Ca²⁺ sensor STIM1 regulates actomyosin contractility of migratory cells.

Author information

  • 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.

PMID:
23378028
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk