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YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.

Zhang J, Wen X, Ren XY, Li YQ, Tang XR, Wang YQ, He QM, Yang XJ, Sun Y, Liu N, Ma J - J. Exp. Clin. Cancer Res. (2016)

Bottom Line: Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT.Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo.The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, People's Republic of China.

ABSTRACT

Background: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored.

Methods: We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting.

Results: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

Conclusions: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.

No MeSH data available.


Related in: MedlinePlus

YPEL3 inhibited the Wnt/β-catenin signaling pathway. a Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 overexpression. b Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 silencing. c YPEL3 inhibited the nuclear (Nu) translocation of β-catenin. Cyto, cytoplasmic. All of the experiments were performed at least three times. Data presented are the mean ± SD; *P < 0.05 and **P < 0.01 compared with control using Student t-test
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Fig6: YPEL3 inhibited the Wnt/β-catenin signaling pathway. a Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 overexpression. b Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 silencing. c YPEL3 inhibited the nuclear (Nu) translocation of β-catenin. Cyto, cytoplasmic. All of the experiments were performed at least three times. Data presented are the mean ± SD; *P < 0.05 and **P < 0.01 compared with control using Student t-test

Mentions: As Wnt/β-catenin plays a critical in EMT induction and maintenance, we examined the protein expression of the Wnt/β-catenin signaling genes for GSK3β, β-catenin, c-MYC, and cyclin D1 in CNE-2 and SUNE-1 cells overexpressing YPEL3 or in which YPEL3 had been silenced to explore the YPEL3 mechanism underlying NPC metastasis. Overexpressing YPEL3 elevated the protein expression of GSK3β and suppressed the protein expression of β-catenin, c-MYC, and cyclin D1(Fig. 6a). Conversely, silencing YPEL3 inhibited the protein expression of GSK3β and increased the protein expression of β-catenin, c-MYC, and cyclin D1 the genes (Fig. 6b). Moreover, subcellular protein fraction study confirmed that YPEL3 overexpression decreased nuclear β-catenin expression and increased cytoplasmic β-catenin expression (Fig. 6c), which indicates that the suppressive effect of YPEL3 may take place through the inhibition of β-catenin nuclear translocation. These data demonstrate that YPEL3 plays a critical role in mediating the Wnt/β-catenin signaling pathway.Fig. 6


YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.

Zhang J, Wen X, Ren XY, Li YQ, Tang XR, Wang YQ, He QM, Yang XJ, Sun Y, Liu N, Ma J - J. Exp. Clin. Cancer Res. (2016)

YPEL3 inhibited the Wnt/β-catenin signaling pathway. a Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 overexpression. b Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 silencing. c YPEL3 inhibited the nuclear (Nu) translocation of β-catenin. Cyto, cytoplasmic. All of the experiments were performed at least three times. Data presented are the mean ± SD; *P < 0.05 and **P < 0.01 compared with control using Student t-test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940860&req=5

Fig6: YPEL3 inhibited the Wnt/β-catenin signaling pathway. a Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 overexpression. b Representative western blotting and quantification analysis of GSK-3β, β-catenin, c-MYC, and cyclin D1 expression levels after YPEL3 silencing. c YPEL3 inhibited the nuclear (Nu) translocation of β-catenin. Cyto, cytoplasmic. All of the experiments were performed at least three times. Data presented are the mean ± SD; *P < 0.05 and **P < 0.01 compared with control using Student t-test
Mentions: As Wnt/β-catenin plays a critical in EMT induction and maintenance, we examined the protein expression of the Wnt/β-catenin signaling genes for GSK3β, β-catenin, c-MYC, and cyclin D1 in CNE-2 and SUNE-1 cells overexpressing YPEL3 or in which YPEL3 had been silenced to explore the YPEL3 mechanism underlying NPC metastasis. Overexpressing YPEL3 elevated the protein expression of GSK3β and suppressed the protein expression of β-catenin, c-MYC, and cyclin D1(Fig. 6a). Conversely, silencing YPEL3 inhibited the protein expression of GSK3β and increased the protein expression of β-catenin, c-MYC, and cyclin D1 the genes (Fig. 6b). Moreover, subcellular protein fraction study confirmed that YPEL3 overexpression decreased nuclear β-catenin expression and increased cytoplasmic β-catenin expression (Fig. 6c), which indicates that the suppressive effect of YPEL3 may take place through the inhibition of β-catenin nuclear translocation. These data demonstrate that YPEL3 plays a critical role in mediating the Wnt/β-catenin signaling pathway.Fig. 6

Bottom Line: Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT.Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo.The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, People's Republic of China.

ABSTRACT

Background: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored.

Methods: We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting.

Results: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin.

Conclusions: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.

No MeSH data available.


Related in: MedlinePlus