HuR translocation to the cytoplasm of cancer cells in actin-independent manner.
HuR translocation to the cytoplasm of cancer cells in actin-independent manner.
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HuR 以不依赖肌动蛋白的方式易位至癌细胞的细胞质。
DOI：
10.1016/j.yexcr.2018.05.021
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Higashino F.
中科院分区：
文献类型：
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作者：
Habiba U.;Kuroshima T.;Yanagawa-Matsuda A.;Kitamura T.;Chowdhury A.;Jehung J.P.;Hossain E.;Sano H.;Kitagawa Y.;Shindoh M.;Higashino F.
人类抗原R(Hur)是一种RNA结合蛋白，它与特定mRNA 3‘-非翻译区富含AU元件(ARE)结合，参与ARE-mRNA的输出和稳定。在许多癌细胞中，HUR结构性地重新定位到细胞质中，然而，HUR在细胞内转运的机制尚不清楚。为了解决这个问题，我们研究了细胞骨架在HUR重新定位中的功能作用。我们测试了肌动蛋白解聚大环内酯类ATPase A或肌球蛋白II ATPase活性抑制剂Blebbistatin对血管活性激素血管紧张素II在癌细胞和对照正常细胞中诱导HUR重新定位的影响。Western印迹和共聚焦成像数据显示，这两种抑制剂都能减弱正常细胞的胞浆HUR，但在癌细胞中没有观察到这种变化。随着Hur在细胞内定位的改变，两种抑制剂都显著减少了Hur靶基因在正常细胞中的积聚和半衰期，而在癌细胞中则没有观察到变化。此外，与HUR蛋白的免疫共沉淀实验显示，只有在正常细胞中才有明显的物理相互作用。目前的研究首次证实癌细胞可以参与微丝独立的HUR运输。我们假设，当细胞骨架结构受损时，癌细胞可以获得另一种Hur转运策略。
Human antigen R (HuR) is a RNA-binding protein, which binds to the AU-rich element (ARE) in the 3′-untranslated region (3′-UTR) of certain mRNA and is involved in the export and stabilization of ARE-mRNA. HuR constitutively relocates to the cytoplasm in many cancer cells, however the mechanism of intracellular HuR trafficking is poorly understood. To address this question, we examined the functional role of the cytoskeleton in HuR relocalization.We tested the effect of actin depolymerizing macrolide latrunculin A or myosin II ATPase activity inhibitor blebbistatin for HuR relocalization induced by the vasoactive hormone Angiotensin II in cancer and control normal cells. Western blot and confocal imaging data revealed that both inhibitors attenuated the cytoplasmic HuR in normal cells but no such alteration was observed in cancer cells. Concomitant with changes in intracellular HuR localization, both inhibitors markedly decreased the accumulation and half-lives of HuR target ARE-mRNAs in normal cells, whereas no change was observed in cancer cells. Furthermore, co-immunoprecipitation experiments with HuR proteins revealed clear physical interaction with ß-actin only in normal cells.The current study is the first to verify that cancer cells can implicate a microfilament independent HuR transport. We hypothesized that when cytoskeleton structure is impaired, cancer cells can acquire an alternative HuR trafficking strategy.