The important role of the receptor for activated C kinase 1 (RACK1) in nasopharyngeal carcinoma progression.
The important role of the receptor for activated C kinase 1 (RACK1) in nasopharyngeal carcinoma progression.
复制标题
活化C激酶1（RACK1）受体在鼻咽癌进展中的重要作用
DOI：
10.1186/s12967-016-0885-x
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发表时间：
2016-05-11
影响因子：
7.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Peng H;Gong PG;Li JB;Cai LM;Yang L;Liu YY;Yao KT;Li X
活化的C激酶1受体（RACK1）参与多种癌症，但其在鼻咽癌（NPC）中的作用尚未完全阐明。方法采用免疫组化方法分析RACK1在鼻咽癌和正常鼻咽癌组织中的表达。并在鼻咽癌细胞中进行qPCR和Western blot检测。用共聚焦显微镜和免疫荧光检测RACK1的亚细胞区室化。随后，在NPC细胞中上调或下调RACK1后，使用体外MTT、EdU、集落形成、Transwell和Boyden试验检测细胞增殖和迁移/侵袭。此外，Western blot检测了几个关键分子，以探索其潜在的机制。最后对临床样本进行分析，确认RACK1表达与临床特征的关系。结果活化的C激酶1受体在鼻咽癌组织中的表达明显高于NP组织。RACK1主要位于细胞质中。RACK1过表达促进了鼻咽癌细胞的增殖和转移/侵袭，而RACK1过表达抑制了鼻咽癌细胞的增殖和转移/侵袭。机制上，RACK1剥夺明显抑制Akt和FAK的激活，提示PI3K/Akt/FAK通路是RACK1在鼻咽癌中的作用机制之一。此外，临床样本分析表明RACK1的体内表达与淋巴结侵袭和鼻咽癌的临床分期呈正相关。结论RACK1蛋白在鼻咽癌的发生发展中起重要作用。RACK1的上调可以通过调控PI3K/Akt/FAK信号通路促进NPC的增殖和侵袭。因此，本研究有助于发现鼻咽癌的潜在治疗靶点。
BackgroundThe receptor for activated C kinase 1 (RACK1) is involved in various cancers, but its roles in nasopharyngeal carcinoma (NPC) have not yet been fully elucidated.MethodsInitially, RACK1 expression was analyzed by immunohistochemistry in NPC and normal nasopharyngeal (NP) tissues. It was also detected by qPCR and Western blot in NPC cells. Confocal microscope and immunofluorescence were performed to detect the subcellular compartmentalization of RACK1. Subsequently, after up- or down-regulating RACK1 in NPC cells, cell proliferation and migration/invasion were tested using in vitro assays including MTT, EdU, colony formation, Transwell and Boyden assays. Furthermore, several key molecules were detected by Western blot to explore underlying mechanism. Finally, clinical samples were analyzed to confirm the relationship between RACK1 expression and clinical features.ResultsReceptor for activated C kinase 1 expression was much higher in NPC than NP tissues. And RACK1 was mainly located in the cytoplasm. Overexpression of RACK1 promoted NPC cell proliferation and metastasis/invasion, whereas depletion of this protein suppressed NPC cell proliferation and metastasis/invasion. Mechanistically, RACK1 deprivation obviously suppressed the activation of Akt and FAK, suggesting the PI3K/Akt/FAK pathway as one of functional mechanisms of RACK1 in NPC. Furthermore, clinical sample analysis indicated a positive correlation between in vivo expression of RACK1 with lymph node invasion and clinical stage of NPC.ConclusionOur results demonstrate that RACK1 protein plays an important role in NPC development and progression. The upregulation of RACK1 can promote the proliferation and invasion of NPC by regulating the PI3K/Akt/FAK signal pathway. Thus, this study contributes to the discovery of a potential therapeutic target for NPC.