Junction plakoglobin, a potential prognostic marker of oral squamous cell carcinoma, promotes proliferation, migration and invasion

Abstract

BackgroundJunction 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.MethodsWe 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.ResultsCox 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.ConclusionThis 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.

Identification of prognostic and bone metastatic alternative splicing signatures in bladder cancer

“…These catenin proteins mediated intercellular interactions and signal transduction between cells [23]. Since JUP is an adhesive protein, the lack of JUP expression can reduce cell-cell contact and increase its proliferation in the body and cancer cells [21]. In this study, by constructing the network of OS-SEs and prognosis-related SFs, we found JUP was one of the Integrin played a major role in signaling networks that promoted angiogenesis and tumor progression [27].…”

“…Junction plakoglobin (JUP, γ-catenin), a member of the armadillo family of proteins [21], is a homolog of β-catenina and forms distinct complexes with cadherins and desmosomal cadherins, which is a key part of the extracellular matrix [22]. These catenin proteins mediated intercellular interactions and signal transduction between cells [23].…”

“…Similar to our results, it was reported that JUP was a crucial SF affecting the metastasis and prognosis of other cancers. In oral squamous cell carcinoma, JUP promoted its proliferation, migration, invasion and was a potential prognostic marker[21]; In breast cancer, loss of JUP would trigger the decreasing contact between cells and the increasing the invasion and spread of breast cancer cells[24]; In addition, Syrigos et al and Rieger et al found that bladder cancer patients with an abnormal expression of JUP always had poor survival status, and the restoration of plakoglobin expression in bladder carcinoma cell lines could inhibit cell migration and tumorigenic potential[25,26].…”

Paradoxical Roles of Desmosomal Components in Head and Neck Cancer

“…The results suggest that these desmosomal components may work as tumor suppressors in HNC. However, the functional study of gain or loss and immunohistochemistry identification of desmosomal components have revealed contradictory roles for some desmosome members, including DSG2 [65,[73][74][75], DSG3 [26,65,66,76], PKP1 [27,77,78], and PG [70,79,83] in HNC, suggesting that the role of the desmosomal components in HNC may be affected by some other signal transduction molecules or/and modifications related to the tumor microenvironment. Additionally, like other tumors, subcellular location, PTM, inactivation by proteolytic cleavage, and the biogenesis of regulating extracellular vesicles (EVs) may also affect the role of desmosomes in HNC.…”

Low expression of plakoglobin in intratumoral liver tissue is associated with poor survival after curative resection of Hepatocellular Carcinoma

“…Recent some studies suggest that plakoglobin acts as a tumor-suppressor protein in some tumors, such as lung primary cancer, prostate cancer and esophageal cancer, its expression in these cancers is very low or completely absent [11,12]. Whereas other studies suggest that plakoglobin has a tumor-inducing effect or oncogenic activity [13][14][15]. It is possible that plakoglobin may have different roles in different malignancies.…”