Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0885-x) contains supplementary material, which is available to authorized users.
Highlights
The receptor for activated C kinase 1 (RACK1) is involved in various cancers, but its roles in nasopharyn‐ geal carcinoma (NPC) have not yet been fully elucidated
The results showed compared to immortalized nasopharyngeal epithelial cell line (NP69), the level of RACK1 mRNA was not significantly increased in NPC cells, even a little decreased in some NPC cells (Fig. 1f )
These results collectively suggest that RACK1 is associated with NPC progression
Summary
The receptor for activated C kinase 1 (RACK1) is involved in various cancers, but its roles in nasopharyn‐ geal carcinoma (NPC) have not yet been fully elucidated. Receptor for activated protein kinase C (RACK1) is an adaptor protein with seven WD40 motifs, 36 kDa, mainly allocated in cytosol and cytoplasmic membrane, providing a scaffold for multiple protein–protein interactions, involving diverse signaling pathways. With regard to its roles in tumorigenesis, RACK1 mainly contributes to tumor growth, invasion and metastasis [9,10,11,12,13,14,15]. Some contradictory results exist in its oncogenic property; this protein can exert a negative control on Src activity [16] and an inhibitory effect on Ki-Ras-mediated morphological cell transformation [17]. The roles of RACK1 in NPC are deserved to be explored
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