Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling

Autor: Jian Ning Wang, Ankui Yang, Xiao Yan Fu, Fan Yao, Qimei Pan, Huayong Zhang, Qiu Li Li, Wei Chao Chen
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Cancer Research
Carcinogenesis
Apoptosis
Receptors
G-Protein-Coupled
Mice
Prognostic marker
0302 clinical medicine
Cell Movement
Receptor
Chemistry
NF-kappa B
Middle Aged
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Tongue Neoplasms
Gene Expression Regulation
Neoplastic
Blot
Leukemia
Oncology
030220 oncology & carcinogenesis
NF-κB signaling
Disease Progression
Receptors
Virus
Immunohistochemistry
Female
Signal Transduction
Epithelial-Mesenchymal Transition
Therapeutic target
Enzyme-Linked Immunosorbent Assay
lcsh:RC254-282
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Biomarkers
Tumor
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Cell Proliferation
Squamous Cell Carcinoma of Head and Neck
Research
Transcription Factor RelA
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Cancer research
Ectopic expression
Xenotropic and Polytropic Retrovirus Receptor
XPR1
TSCC
Zdroj: Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-12 (2019)
Journal of Experimental & Clinical Cancer Research : CR
ISSN: 1756-9966
Popis: Background Xenotropic 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. Methods Real-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. Results Herein, 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. Conclusions These 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. Electronic supplementary material The online version of this article (10.1186/s13046-019-1155-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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