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.

USP22 drives colorectal cancer invasion and metastasis via epithelial-mesenchymal transition by activating AP4

“…Our results also demonstrated that USP22 can increase cell migration and invasion abilities via EMT induction. According to the results of previous studies, USP22 can induce EMT by regulating TGF-β1 in lung cancer cells [8], and elevated USP22 expression can promote EMT by up-regulating ZEB1 and Snail in pancreatic cancer cells though a process that involves focal adhesion kinase (FAK) signaling [29]. The present study has revealled an additional novel mechanism by which USP22 induces EMT.…”

Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation

“…Phosphorylation and dephosphorylation of Ezrin at T567 has been identified as a critical step in the conformational activation and deactivation of Ezrin [44]. Our previous studies confirmed that phosphorylated Ezrin could mediate EMT in pancreatic cancer cells through the FAK pathway and promote invasion and metastasis [45]. In this study, during the EMT induced by TCM, Ezrin phosphorylation (T567) increased significantly (Figure 4A), which is similar to the expression of FUT4/LeY (Figure 2B).…”

Reduced Expression of Adherens Junctions Associated Protein 1 Predicts Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy

“…[47][48][49] Activation of the SRC tyrosine kinase facilitates EMT through the FAK and phosphatidyl inositol-3 kinase signaling pathways. 50 Our present results suggest that AJAP1 mediated the EMT of HCC cells through regulation of SRC transcription and its related signaling pathways. Further investigation of the correlation between the expression of AJAP1 and EMT-associated molecules is required to understand HCC pathogenesis.…”