Among gynecological cancers, ovarian carcinoma has the highest mortality rate, and chemoresistance is highly prevalent in this cancer. Therefore, novel strategies are required to improve its poor prognosis. Formation and disassembly of focal adhesions are regulated dynamically during cell migration, which plays an essential role in cancer metastasis. Metastasis is intricately linked with resistance to chemotherapy, but the molecular basis for this link is unknown. Transwell migration and wound healing migration assays were used to analyze the migration ability of ovarian cancer cells. Real-time recordings by total internal reflection fluorescence microscope (TIRFM) were performed to assess the turnover of focal adhesions with fluorescence protein-tagged focal adhesion molecules. SOCE inhibitors were used to verify the effects of SOCE on focal adhesion dynamics, cell migration, and chemoresistance in chemoresistant cells. We found that mesenchymal-like chemoresistant IGROV1 ovarian cancer cells have higher migration properties because of their rapid regulation of focal adhesion dynamics through FAK, paxillin, vinculin, and talin. Focal adhesions in chemoresistant cells, they were smaller and exhibited strong adhesive force, which caused the cells to migrate rapidly. Store-operated Ca2+ entry (SOCE) regulates focal adhesion turnover, and cell polarization and migration. Herein, we compared SOCE upregulation in chemoresistant ovarian cancer cells to its parental cells. SOCE inhibitors attenuated the assembly and disassembly of focal adhesions significantly. Results of wound healing and transwell assays revealed that SOCE inhibitors decreased chemoresistant cell migration. Additionally, SOCE inhibitors combined with chemotherapeutic drugs could reverse ovarian cancer drug resistance. Our findings describe the role of SOCE in chemoresistance-mediated focal adhesion turnover, cell migration, and viability. Consequently, SOCE might be a promising therapeutic target in epithelial ovarian cancer.

中文翻译：

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耐化学性卵巢癌通过增加存储操纵的Ca ²⁺进入介导的粘着斑转换来增强其迁移能力

在妇科癌症中，卵巢癌的死亡率最高，化学耐药性在该癌症中非常普遍。因此，需要新的策略来改善其不良预后。粘着斑的形成和分解在细胞迁移过程中受到动态调节，这在癌症转移中起着至关重要的作用。转移与对化学疗法的抵抗力有着复杂的联系，但是这种联系的分子基础尚不清楚。Transwell迁移和伤口愈合迁移分析用于分析卵巢癌细胞的迁移能力。通过全内反射荧光显微镜（TIRFM）进行实时记录，以评估带有荧光蛋白标签的粘着斑分子的粘着斑的周转率。使用SOCE抑制剂来验证SOCE对化学耐药细胞中粘着动力学，细胞迁移和化学抗性的影响。我们发现间充质样化学抗性IGROV1卵巢癌细胞具有较高的迁移特性，因为它们通过FAK，paxillin，vincinin和talin快速调节粘着斑动态。耐化学性细胞中的粘着斑较小，并且表现出很强的粘附力，这导致细胞快速迁移。商店经营的Ca2 +进入（SOCE）调节粘着斑转换，细胞极化和迁移。在本文中，我们比较了化学抗性卵巢癌细胞与其亲代细胞中SOCE的上调。SOCE抑制剂可显着减弱粘着斑的组装和拆卸。伤口愈合和transwell分析的结果表明，SOCE抑制剂可降低化学抗性细胞的迁移。此外，SOCE抑制剂与化学治疗药物联合可以逆转卵巢癌药物耐药性。我们的发现描述了SOCE在化学抗性介导的粘着粘附更新，细胞迁移和生存力中的作用。因此，SOCE可能是上皮性卵巢癌的有希望的治疗靶标。