USP22 promotes epithelial-mesenchymal transition via the FAK pathway in pancreatic cancer cells

Ning,Zhen; Wang,Aman; Liang,Jinxiao; Xie,Yunpeng; Liu,Jiwei; Yan,Qiu; Wang,Zhongyu

doi:10.3892/or.2014.3354

USP22 promotes epithelial-mesenchymal transition via the FAK pathway in pancreatic cancer cells

Authors:
- Zhen Ning
- Aman Wang
- Jinxiao Liang
- Yunpeng Xie
- Jiwei Liu
- Qiu Yan
- Zhongyu Wang
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Affiliations: Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China, Department of Oncology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China, Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian, Liaoning, P.R. China
Published online on: July 23, 2014 https://doi.org/10.3892/or.2014.3354
Pages: 1451-1458

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Abstract

Epithelial-mesenchymal transition (EMT) contributes to the occurrence and development of tumors, particularly to the promotion of tumor invasion and metastasis. As a newly discovered ubiquitin hydrolase family member, USP22 plays a key role in the malignant transformation of tumors and the regulation of the cell cycle. However, recent studies on USP22 have primarily focused on its role in cell cycle regulation, and the potential mechanism underlying the promotion of tumor invasion and metastasis by abnormal USP22 expression has not been reported. Our studies revealed that the overexpression of USP22 in PANC-1 cells promoted Ezrin redistribution and phosphorylation and cytoskeletal remodeling, upregulated expression of the transcription factors Snail and ZEB1 to promote EMT, and increased cellular invasion and migration. In contrast, blockade of USP22 expression resulted in the opposite effects. In addition, the focal adhesion kinase (FAK) signaling pathway was shown to play a key role in the process of EMT induction in PANC-1 cells by USP22. Thus, the present study suggests that USP22 acts as a regulatory protein for EMT in pancreatic cancer, which may provide a new approach for the targeted therapy of pancreatic cancer.

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