Abstract
BackgroundXenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized.MethodsReal-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay.ResultsHerein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens.ConclusionsThese findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.
Highlights
Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes
XPR1 overexpression correlates with progression and poor prognosis in Tongue squamous cell carcinoma (TSCC) To investigate the role of XPR1 in cancer, we first analyze its expression
Analysis with the Cancer Genome Atlas (TCGA) Head and Neck Cancer (HNSCC) dataset suggested that XPR1 was robustly increased in tumor samples compared to normal tissues (Additional file 1: Figure S1A)
Summary
Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. Despite considerable advances in diagnostics and therapies for this disease, the overall 5-year survival rate for OSCC patients stuck around 50% without marked improvement, because of the high risks of developing secondary or recurrent tumors in surrounding area [6,7,8,9]. Xenotropic and polytropic retrovirus receptor (XPR1) is a 696-amino acid protein with multiple transmembrane-spanning domains It was first identified as a specific cell-surface receptor for xenotropic and polytropic classes of murine leukemia viruses (MLV) [10,11,12]. Based on its homology to proteins involved in the regulation of phosphate transport, including PHO1, PHO90, and PHO91 [16,17,18], XPR1 has been identified as an inorganic phosphate exporter in human cells [19]
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