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

Ying Ting Chen, Yih Fung Chen, Wen Tai Chiu, Yang Kao Wang, Hsien Chang Chang, Meng Ru Shen

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum (ER) Ca2+ sensor that triggers the store-operated Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ signaling in controlling cell migration by the regulation of actomyosin reorganization in conjunction with enhanced contractile forces.

Original languageEnglish
Pages (from-to)1260-1267
Number of pages8
JournalJournal of Cell Science
Volume126
Issue number5
DOIs
Publication statusPublished - Mar 1 2013

    Fingerprint

Keywords

  • Actomyosin
  • Contractile force
  • Microfabricated post-array detectors
  • Stromal-interaction molecule 1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Chen, Y. T., Chen, Y. F., Chiu, W. T., Wang, Y. K., Chang, H. C., & Shen, M. R. (2013). The ER Ca2+ sensor STIM1 regulates actomyosin contractility of migratory cells. Journal of Cell Science, 126(5), 1260-1267. https://doi.org/10.1242/jcs.121129