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RNF128 Promotes Invasion and Metastasis Via the EGFR/MAPK/MMP-2 Pathway in Esophageal Squamous Cell Carcinoma

Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
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Cancers 2019, 11(6), 840; https://doi.org/10.3390/cancers11060840
Received: 5 May 2019 / Revised: 5 June 2019 / Accepted: 12 June 2019 / Published: 18 June 2019
Background: The prognosis of esophageal squamous cell carcinoma (ESCC) is generally poor, and the identification of molecular markers related to the regulation of ESCC invasion and migration is important. Methods and Results: In this study, we report that ring finger protein-128 (RNF128) enhances the invasiveness and motility of ESCC cells by using transwell assays and Western blotting. A xenograft nude mouse model showed that RNF128 promotes the metastasis of ESCC cells in the lung. A signal pathway analysis identified the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/matrix matalloproteinases 2 (MMP-2) cascade as a mediator of RNF128-induced enhancement of ESCC progression. Inhibition experiments using inhibitors of EGFR, ERK kinase (MEK)/extracellular-signal-regulated-kinase (ERK), and MMP-2 reversed this progression. Co-immunoprecipitation demonstrated that RNF128 promotes the activation of the EGFR/ERK/MMP-2 pathway by interacting with p53 and p53 interacting with EGFR. Conclusion: Our results establish the functional role of RNF128 in driving the invasion and metastasis of ESCC through the EGFR/MAPK/MMP-2 pathway, implicating its potential as a candidate therapeutic target and prognostic biomarker for ESCC. View Full-Text
Keywords: ESCC; RNF128; migration; invasion; MMP-2 ESCC; RNF128; migration; invasion; MMP-2
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Gao, J.; Wang, Y.; Yang, J.; Zhang, W.; Meng, K.; Sun, Y.; Li, Y.; He, Q.-Y. RNF128 Promotes Invasion and Metastasis Via the EGFR/MAPK/MMP-2 Pathway in Esophageal Squamous Cell Carcinoma. Cancers 2019, 11, 840.

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