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Concerted Modulation of Paxillin Dynamics at Focal Adhesions by Deleted in Liver Cancer-1 and Focal Adhesion Kinase During Early Cell Spreading

机译:肝细胞癌早期扩散过程中肝癌1和局部黏着斑激酶缺失后局部黏着斑上Paxillin动力学的协同调节

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摘要

Deleted in Liver Cancer-1 (DLC1) is a RhoGTPase-activating protein (GAP) and a tumor suppressor often downregulated in cancers. It is localized to the focal adhesions (FAs) and its absence leads to enhanced cell migration, invasion, and metastasis. Although DLC1 interacts with focal adhesion kinase (FAK), talin, and tensin, its role in focal adhesions dynamics remains unclear. We examined the effect of DLC1 in Human Foreskin Fibroblasts and determined its localization, dynamics and impact on paxillin by Fluorescence Recovery After Photobleaching at both nascent and mature focal adhesions. During early cell spreading, DLC1 is preferentially localized at the inner/mature adhesions whereas phosphorylated paxillin occupies the outerascent FAs. In addition, DLC1 downregulates paxillin turnover in a process, that does not require its GAP activity. Instead, it requires the presence of FAK. Acting in concert, both DLC1 and FAK could provide a unique spatio-temporal mechanism to regulate paxillin function in tissue homeostasis. (C) 2014 Wiley Periodicals, Inc.
机译:RhoGTPase激活蛋白(GAP)在肝癌1(DLC1)中被删除,并且在癌症中常常被下调。它位于粘着斑(FAs)处,并且不存在会导致细胞迁移,侵袭和转移增强。尽管DLC1与粘着斑激酶(FAK),塔林和张力蛋白相互作用,但其在粘着斑动力学中的作用仍不清楚。我们检查了DLC1在人包皮成纤维细胞中的作用,并通过新生和成熟粘着斑光漂白后的荧光恢复测定了其定位,动力学和对paxillin的影响。在早期细胞扩散过程中,DLC1优先定位在内部/成熟的粘连处,而磷酸化的Paxillin则占据外部/新生的FA。此外,DLC1在不需要其GAP活性的过程中下调了Paxillin的转化。相反,它需要存在FAK。 DLC1和FAK共同发挥作用,可以提供独特的时空机制来调节组织动态平衡中的Paxillin功能。 (C)2014威利期刊公司

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