PDF(Pubmed)
Abstract：
BACKGROUND: The intermediate filament protein vimentin is widely recognized as a molecular marker of epithelial-to-mesenchymal transition. Although vimentin expression is strongly associated with cancer metastatic potential, the exact role of vimentin in cancer metastasis and the underlying mechanism of its pro-metastatic functions remain unclear.
RESULTS: This study revealed that vimentin can enhance integrin β1 surface expression and induce integrin-dependent clustering of cells, shielding them against anoikis cell death. The increased integrin β1 surface expression in suspended cells was caused by vimentin-mediated protection of the internal integrin β1 pool against lysosomal degradation. Additionally, cell detachment was found to induce vimentin Ser38 phosphorylation, allowing the translocation of internal integrin β1 to the plasma membrane. Furthermore, the use of an inhibitor of p21-activated kinase PAK1, one of the kinases responsible for vimentin Ser38 phosphorylation, significantly reduced cancer metastasis in animal models.
CONCLUSIONS: These findings suggest that vimentin can act as an integrin buffer, storing internalized integrin β1 and releasing it when needed. Overall, this study provides insights regarding the strong correlation between vimentin expression and cancer metastasis and a basis for blocking metastasis using this novel therapeutic mechanism.
RESULTS: This study revealed that vimentin can enhance integrin β1 surface expression and induce integrin-dependent clustering of cells, shielding them against anoikis cell death. The increased integrin β1 surface expression in suspended cells was caused by vimentin-mediated protection of the internal integrin β1 pool against lysosomal degradation. Additionally, cell detachment was found to induce vimentin Ser38 phosphorylation, allowing the translocation of internal integrin β1 to the plasma membrane. Furthermore, the use of an inhibitor of p21-activated kinase PAK1, one of the kinases responsible for vimentin Ser38 phosphorylation, significantly reduced cancer metastasis in animal models.
CONCLUSIONS: These findings suggest that vimentin can act as an integrin buffer, storing internalized integrin β1 and releasing it when needed. Overall, this study provides insights regarding the strong correlation between vimentin expression and cancer metastasis and a basis for blocking metastasis using this novel therapeutic mechanism.
摘要：
背景：中间丝蛋白波形蛋白被广泛认为是上皮-间质转化的分子标志物。尽管波形蛋白表达与癌症转移潜力密切相关，波形蛋白在癌症转移中的确切作用及其促转移功能的潜在机制尚不清楚.
结果：本研究显示波形蛋白能增强整合素β1的表面表达，诱导整合素依赖性的细胞聚集，保护他们免受anoikis细胞死亡。悬浮细胞中整合素β1表面表达的增加是由波形蛋白介导的内部整合素β1库针对溶酶体降解的保护作用引起的。此外,发现细胞脱离诱导波形蛋白Ser38磷酸化，允许内部整合素β1易位到质膜。此外，使用p21激活的激酶PAK1的抑制剂，PAK1是负责波形蛋白Ser38磷酸化的激酶之一，在动物模型中显著减少癌症转移。
结论：这些发现表明波形蛋白可以作为整合素缓冲液，储存内化整合素β1并在需要时释放。总的来说,这项研究提供了关于波形蛋白表达与癌症转移之间强相关性的见解，以及使用这种新的治疗机制阻断转移的基础。
结果：本研究显示波形蛋白能增强整合素β1的表面表达，诱导整合素依赖性的细胞聚集，保护他们免受anoikis细胞死亡。悬浮细胞中整合素β1表面表达的增加是由波形蛋白介导的内部整合素β1库针对溶酶体降解的保护作用引起的。此外,发现细胞脱离诱导波形蛋白Ser38磷酸化，允许内部整合素β1易位到质膜。此外，使用p21激活的激酶PAK1的抑制剂，PAK1是负责波形蛋白Ser38磷酸化的激酶之一，在动物模型中显著减少癌症转移。
结论：这些发现表明波形蛋白可以作为整合素缓冲液，储存内化整合素β1并在需要时释放。总的来说,这项研究提供了关于波形蛋白表达与癌症转移之间强相关性的见解，以及使用这种新的治疗机制阻断转移的基础。
