STIM1 Controls the Focal Adhesion Dynamics and Cell Migration by Regulating SOCE in Osteosarcoma

International Journal of Molecular Sciences

Yi-Hsin Lin¹  MyHang Nguyen Thi¹  Shih-Chuan Hsiao²  Yu-Shan Lin³  Wen-Tai Chiu³ 

[1] Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan;Department of Hematology & Oncology, Saint Martin de Porres Hospital, Chiayi 600, Taiwan;Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan;

关键词: STIM1;    SOCE;    focal adhesion;    cell migration;   

DOI  :  10.3390/ijms23010162

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown