Volume 29 Issue 4 - June 5, 2015 PDF
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Endoplasmic reticulum Ca2+ sensor STIM1 regulates actomyosin contractility of migratory cells
Ying-Ting Chen1, Yih-Fung Chen2, Wen-Tai Chiu1, 3, Yang-Kao Wang4, 5, Hsien-Chang Chang1, 5, Meng-Ru Shen2, 6, 7, 8,*
1 Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan
2 Department of Pharmacology, National Cheng Kung University, Tainan 701, Taiwan
3 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan
4 Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei 110, Taiwan
5 Medical Device Innovation Center, National Cheng Kung University, Tainan 701, Taiwan
6 Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan 704, Taiwan
7 Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan 701, Taiwan
 
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Modulation of intracellular Ca2+ levels provides versatile and dynamic signaling that mediates various cellular processes, such as proliferation, migration, and gene expression. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx in non-excitable cells, and the major molecular components in regulation of SOCE are the ER Ca2+ sensor stromal interaction molecule1 (STIM1) and two plasma membrane Ca2+ channels transient receptor potential channel 1 (TRPC1) and Orai1. The clinical relevance of STIM1 has been highlighted in breast and cervical cancer. In this report, we explored the regulatory mechanisms by which STIM1-dependent Ca2+ signaling controls cancer cell migration. SOCE inhibitor SKF96365 significantly inhibited cervical cancer cell migration to a similar extent by STIM1 silencing. 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 inhibitor. Most importantly, STIM1 expression levels as well as SOCE activity controlled the generation of cell contractile force, measured by the microfabricated post-array-detector system. These results highlight the unique role of STIM1-dependent Ca2+ signalings in controlling cell migration by the regulation of actomyosin reorganization in conjunction with enhanced contractile forces.

Figure 1. Measurement the contractile force on each adhesion site by an microfabricated post-array-detector (mPAD). Upper panel, cross section of a 3D image of the top of a micropillar showing that a cell contracts and pulls the adherent micropillar. Lower panel, the ontractile forces (F) on a single adhesion site were calculated using the displacement (ΔX) and spring constant of a micropillar; E, Young’s modulus; D, diameter; L, length and ΔX, deflection of the micropillar.
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