Schmidt Anette, Kaakinen Mika, Wenta Tomasz, Manninen Aki
Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Front Cell Dev Biol. 2022 Jul 7;10:886569. doi: 10.3389/fcell.2022.886569. eCollection 2022.
Epithelial cell adhesion is mediated by actin cytoskeleton-linked focal adhesions (FAs) and intermediate filament-associated hemidesmosomes (HDs). HDs are formed by α6β4-integrins and mediate stable anchoring to the extracellular matrix (ECM) while FAs containing β1-integrins regulate cell migration. Loss of HDs has been reported in various cancers such as prostate cancer where it correlates with increased invasive migration. Here we have studied cell migration properties and FA dynamics in genetically engineered prostate epithelial cell lines with intact or disrupted HDs. Disruption of HDs by depleting α6- or β4-integrin expression promoted collective cell migration and modulated migratory activity. Dynamic analysis of fluorescent protein-tagged FA marker proteins revealed faster FA assembly and disassembly kinetics in HD-depleted cells. FRAP analysis showed that loss of HDs correlated with faster diffusion rates of focal adhesion kinase (FAK) and vinculin in and out of FAs. These data suggest that loss of α6β4-mediated HDs promote cell migration and FA assembly dynamics by influencing the molecular diffusion rates of FAK.
上皮细胞黏附由肌动蛋白细胞骨架连接的黏着斑（FAs）和中间丝相关的半桥粒（HDs）介导。HDs由α6β4整合素形成，介导与细胞外基质（ECM）的稳定锚定，而含有β1整合素的FAs调节细胞迁移。HDs缺失在多种癌症中都有报道，如前列腺癌，其与侵袭性迁移增加相关。在这里，我们研究了具有完整或破坏HDs的基因工程前列腺上皮细胞系中的细胞迁移特性和FA动态。通过耗尽α6或β4整合素表达来破坏HDs，促进了集体细胞迁移并调节了迁移活性。对荧光蛋白标记的FA标记蛋白的动态分析显示，HD缺失细胞中FA组装和解聚动力学更快。FRAP分析表明，HDs缺失与黏着斑激酶（FAK）和纽蛋白进出FAs的更快扩散速率相关。这些数据表明，α6β4介导的HDs缺失通过影响FAK的分子扩散速率来促进细胞迁移和FA组装动态。
