title: USP22 promotes epithelial-mesenchymal transition via the FAK pathway in pancreatic cancer cells.
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.
authors: Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China.
authors: Zhen
authors: Z
authors: Ning
authors: Department of Oncology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China.
authors: Aman
authors: A
authors: Wang
authors: Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China.
authors: Jinxiao
authors: J
authors: Liang
authors: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian, Liaoning, P.R. China.
authors: Yunpeng
authors: Y
authors: Xie
authors: Department of Oncology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China.
authors: Jiwei
authors: J
authors: Liu
authors: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian, Liaoning, P.R. China.
authors: Qiu
authors: Q
authors: Yan
authors: Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China.
authors: Zhongyu
authors: Z
authors: Wang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013869:Thiolester Hydrolases / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D051417:Focal Adhesion Kinase 1; D018398:Homeodomain Proteins; D000071250:Snail Family Transcription Factors; D013869:Thiolester Hydrolases; D014157:Transcription Factors; D043222:Ubiquitin Thiolesterase; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000099149:Ezrin; C486307:ZEB1 protein, human; C496050:PTK2 protein, human; C527170:Usp22 protein, human