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JUP, a homologue of β-catenin, is a cell-cell junction protein involved in adhesion junction and desmosome composition. JUP may have a controversial role in different malignancies dependence of its competence with or collaboration with β-catenin as a transcription factor. In this study, we focused on the role of JUP in tumor progress and metastasis of GC. We investigated whether that the function of JUP is related to its cellular location in GC development process from epithelium-like, low malignant GC to advanced EMT-phenotypic GC. Gradual loss of membrane and/or cytoplasm JUP was closely correlated with GC malignancy and poor prognostics. Knockdown of JUP in epithelium-like GC cells causes EMT and promotes GC cell migration and invasion. Ectopic expression of wild JUP in malignant GC cells led to an attenuated malignant phenotype such as reduced cell invasive potential. In mechanism, loss of membrane and/or cytoplasm JUP abolished the restrain of JUP to EGFR at cell membrane and resulted in increased p-AKT levels and AKT/GSK3β/β-catenin signaling activity. In addition, nuclear JUP interacts with nuclear β-catenin and TCF4 and played a synergistic role with β-catenin in promoting TCF4 transcription and its downstream target MMP7 expression to fuel GC cell invasion. [ABSTRACT FROM AUTHOR]

Background: Junction plakoglobin (JUP) is an important cell-cell junction protein. Recently, its deregulation has been correlated with the initiation and progression of various malignancies. Our aim was to investigate the expression of JUP in oral squamous cell carcinoma (OSCC) and its correlation with prognosis and to further study the effects of JUP on the proliferation, apoptosis, migration and invasion of OSCC cells.Methods: We detected JUP expression in 273 OSCC specimens using immunohistochemistry. We assessed the correlation of JUP expression with clinicopathologic parameters and patient survival by Cox regression. Then, expression levels of JUP in normal oral keratinocytes (NOKs) and OSCC cell lines were detected by Western blotting and quantitative real-time PCR (qPCR). Next, we used HSC3 cells to study the effect of JUP on tumor cell proliferation, apoptosis, migration, and invasion by using cell counting kit-8, flow cytometry, and transwell assays, respectively.Results: Cox regression showed that high expression of JUP was related to the poor prognosis of OSCC patients. Western blotting and qPCR assays showed that the expression level of JUP in OSCC cell lines was higher than that in NOKs. Overexpression of JUP promoted the proliferation, metastasis, and invasion of HSC3 cells and inhibited apoptosis, while the opposite was observed after JUP knockdown.Conclusion: This study initially revealed that JUP was overexpressed in OSCC, and that JUP promoted the proliferation, migration, and invasion of OSCC cells and inhibited apoptosis. Moreover, high expression of JUP could be used as a potential prognostic marker of OSCC. [ABSTRACT FROM AUTHOR]