Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ijms23010162
Keywords
STIM1; SOCE; focal adhesion; cell migration
Funding
- Ministry of Science and Technology of Taiwan [110-2628-B-006-030]
- [STIM1-D76A-EYFP]
- [110-2320-B-006-060]
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The dysregulation of store-operated Ca2+ entry (SOCE) is associated with cancer progression. Upregulation of stromal interaction molecule 1 (STIM1) promotes cancer cell migration, invasion, and metastasis, while excessive Ca2+ can have a negative impact on cancer metastasis.
The dysregulation of store-operated Ca2+ entry (SOCE) promotes cancer progression by changing Ca2+ levels in the cytosol or endoplasmic reticulum. Stromal interaction molecule 1 (STIM1), a component of SOCE, is upregulated in several types of cancer and responsible for cancer cell migration, invasion, and metastasis. To explore the impact of STIM1-mediated SOCE on the turnover of focal adhesion (FA) and cell migration, we overexpressed the wild-type and constitutively active or dominant negative variants of STIM1 in an osteosarcoma cell line. In this study, we hypothesized that STIM1-mediated Ca2+ elevation may increase cell migration. We found that constitutively active STIM1 dramatically increased the Ca2+ influx, calpain activity, and turnover of FA proteins, such as the focal adhesion kinase (FAK), paxillin, and vinculin, which impede the cell migration ability. In contrast, dominant negative STIM1 decreased the turnover of FA proteins as its wild-type variant compared to the cells without STIM1 overexpression while promoting cell migration. These unexpected results suggest that cancer cells need an appropriate amount of Ca2+ to control the assembly and disassembly of focal adhesions by regulating calpain activity. On the other hand, overloaded Ca2+ results in excessive calpain activity, which is not beneficial for cancer metastasis.
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