Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan.
Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan.
Int J Mol Sci. 2021 Dec 23;23(1):162. doi: 10.3390/ijms23010162.
The dysregulation of store-operated Ca entry (SOCE) promotes cancer progression by changing Ca 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 Ca elevation may increase cell migration. We found that constitutively active STIM1 dramatically increased the Ca 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 Ca to control the assembly and disassembly of focal adhesions by regulating calpain activity. On the other hand, overloaded Ca results in excessive calpain activity, which is not beneficial for cancer metastasis.
钙库操纵的钙内流（SOCE）的失调通过改变细胞质或内质网中的钙水平来促进癌症的进展。SOCE 的一个组成部分基质相互作用分子 1（STIM1）在几种类型的癌症中上调，负责癌细胞的迁移、侵袭和转移。为了探讨 STIM1 介导的 SOCE 对焦点黏附（FA）和细胞迁移的周转率的影响，我们在骨肉瘤细胞系中过表达了野生型和组成型激活或显性负变体的 STIM1。在这项研究中，我们假设 STIM1 介导的钙升高可能会增加细胞迁移。我们发现组成型激活的 STIM1 显著增加了钙内流、钙蛋白酶活性和 FA 蛋白（如粘着斑激酶（FAK）、桩蛋白和 vinculin）的周转率，这会阻碍细胞迁移能力。相比之下，与没有 STIM1 过表达的细胞相比，显性负 STIM1 降低了 FA 蛋白的周转率，同时促进了细胞迁移。这些出乎意料的结果表明，癌细胞需要适量的钙来通过调节钙蛋白酶活性来控制焦点黏附的组装和拆卸。另一方面，过载的钙会导致钙蛋白酶活性过度，这不利于癌症转移。
