PRMT5 promotes epithelial‐mesenchymal transition via EGFR‐β‐catenin axis in pancreatic cancer cells

Autor: Xiao Xu, Min Xu, Wanxin Peng, Fengyi Du, Junbo He, Huizhi Wang, Youli Zhang, Lu Ge, Aihua Gong, Zhengrong Zhou
Rok vydání: 2019
Předmět:
0301 basic medicine
Protein-Arginine N-Methyltransferases
Epithelial-Mesenchymal Transition
Carcinogenesis
EGFR
Mice
Nude
Vimentin
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line
Tumor
Pancreatic cancer
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Protein kinase B
protein arginine methyltransferase 5
beta Catenin
Cell Proliferation
Mice
Inbred BALB C
epithelial‐mesenchymal transition
biology
Chemistry
AKT
Protein arginine methyltransferase 5
GSK3β
Original Articles
Cell Biology
medicine.disease
ErbB Receptors
Gene Expression Regulation
Neoplastic
Pancreatic Neoplasms
030104 developmental biology
030220 oncology & carcinogenesis
Catenin
Cancer research
biology.protein
β‐catenin
Molecular Medicine
Original Article
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.14894
Popis: Protein arginine methyltransferase 5 (PRMT5) has been implicated in the development and progression of human cancers. However, few studies reveal its role in epithelial‐mesenchymal transition (EMT) of pancreatic cancer cells. In this study, we find that PRMT5 is up‐regulated in pancreatic cancer, and promotes proliferation, migration and invasion in pancreatic cancer cells, and promotes tumorigenesis. Silencing PRMT5 induces epithelial marker E‐cadherin expression and down‐regulates expression of mesenchymal markers including Vimentin, collagen I and β‐catenin in PaTu8988 and SW1990 cells, whereas ectopic PRMT5 re‐expression partially reverses these changes, indicating that PRMT5 promotes EMT in pancreatic cancer. More importantly, we find that PRMT5 knockdown decreases the phosphorylation level of EGFR at Y1068 and Y1172 and its downstream p‐AKT and p‐GSK3β, and then results in down‐regulation of β‐catenin. Expectedly, ectopic PRMT5 re‐expression also reverses the above changes. It is suggested that PRMT5 promotes EMT probably via EGFR/AKT/β‐catenin pathway. Taken together, our study demonstrates that PRMT5 plays oncogenic roles in the growth of pancreatic cancer cell and provides a potential candidate for pancreatic cancer treatment.
Databáze: OpenAIRE
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