Hypoxia-induced invadopodia formation involves activation of NHE-1 by the p90 ribosomal S6 kinase (p90RSK).
Hypoxia-induced invadopodia formation involves activation of NHE-1 by the p90 ribosomal S6 kinase (p90RSK).
复制标题
缺氧诱导的Intopodia形成涉及P90核糖体S6激酶（P90RSK）激活NHE-1。
DOI：
10.1371/journal.pone.0028851
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Dubois CM
中科院分区：
文献类型：
--
作者：
Lucien F;Brochu-Gaudreau K;Arsenault D;Harper K;Dubois CM
肿瘤中的缺氧和酸性微环境与恶性进展和转移密切相关，因此已成为肿瘤生理学和癌症治疗的中心问题。尽管如此，酸性pH和缺氧介导的细胞侵袭/转移之间的分子联系仍然大多未得到解决。肿瘤细胞用于组织侵袭的机制之一是侵袭伪足的产生，侵袭伪足是降解细胞外基质的富含肌动蛋白的侵袭性质膜突起。在这里，我们表明，缺氧刺激侵袭伪足的形成以及癌细胞的侵袭能力。Na+/H+交换器NHE-1的抑制或基于shRNA的消耗，沿着通过活细胞成像进行的细胞内pH监测，揭示侵袭伪足形成与细胞pH稳态的改变相关，这是一个涉及NHE-1激活Na+/H+交换速率的事件。进一步的表征表明，缺氧触发了p90核糖体S6激酶（p90 RSK）的激活，这导致侵袭伪足形成和NHE-1的位点特异性磷酸化和激活。这项研究揭示了p90 RSK在肿瘤细胞侵袭中的作用，并建立了p90 RS激酶作为缺氧和肿瘤酸性微环境之间的联系。
The hypoxic and acidic microenvironments in tumors are strongly associated with malignant progression and metastasis, and have thus become a central issue in tumor physiology and cancer treatment. Despite this, the molecular links between acidic pH- and hypoxia-mediated cell invasion/metastasis remain mostly unresolved. One of the mechanisms that tumor cells use for tissue invasion is the generation of invadopodia, which are actin-rich invasive plasma membrane protrusions that degrade the extracellular matrix. Here, we show that hypoxia stimulates the formation of invadopodia as well as the invasive ability of cancer cells. Inhibition or shRNA-based depletion of the Na+/H+ exchanger NHE-1, along with intracellular pH monitoring by live-cell imaging, revealed that invadopodia formation is associated with alterations in cellular pH homeostasis, an event that involves activation of the Na+/H+ exchange rate by NHE-1. Further characterization indicates that hypoxia triggered the activation of the p90 ribosomal S6 kinase (p90 RSK), which resulted in invadopodia formation and site-specific phosphorylation and activation of NHE-1. This study reveals an unsuspected role of p90RSK in tumor cell invasion and establishes p90RS kinase as a link between hypoxia and the acidic microenvironment of tumors.
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影响因子：
4.1
作者：
Frödin, M;Gammeltoft, S
通讯作者：
Gammeltoft, S
DOI：
10.1161/01.atv.0000258979.92828.bc
发表时间：
2007-04-01
影响因子：
8.7
作者：
Bonello, Steve;Zahringer, Christian;Goerlach, Agnes
通讯作者：
Goerlach, Agnes
DOI：
10.1159/000468616
发表时间：
1996-01-01
期刊：
ENZYME & PROTEIN
影响因子：
--
作者：
Chen, WT
通讯作者：
Chen, WT
影响因子：
4.6
作者：
Corvera, JS;Zhao, ZQ;Vinten-Johansen, J
通讯作者：
Vinten-Johansen, J
DOI：
10.1111/j.1582-4934.2008.00568.x
发表时间：
2009-08-01
影响因子：
5.3
作者：
Caldieri, Giusi;Giacchetti, Giada;Buccione, Roberto
通讯作者：
Buccione, Roberto