PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell Lung Cancer

• Published in: The Journal of biological chemistry Vol. 290; no. 21; pp. 13479 - 13489
• Main Authors: Avasarala, Sreedevi, Van Scoyk, Michelle, Karuppusamy Rathinam, Manoj Kumar, Zerayesus, Sereke, Zhao, Xiangmin, Zhang, Wei, Pergande, Melissa R., Borgia, Jeffrey A., DeGregori, James, Port, J. David, Winn, Robert A., Bikkavilli, Rama Kamesh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.05.2015; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Arginine - genetics; Blotting, Western; cadherin-1 (CDH1) (epithelial cadherin) (E-cadherin); Cadherins - genetics; Cadherins - metabolism; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - secondary; Cell Movement; Cell Proliferation; DNA Methylation; Epithelial-Mesenchymal Transition; epithelial-mesenchymal transition (EMT); Fluorescent Antibody Technique, Indirect; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; metastasis; Mice; Molecular Bases of Disease; Molecular Sequence Data; N-cadherin; Neoplasm Invasiveness; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Prmt1; protein methylation; Protein-Arginine N-Methyltransferases - antagonists & inhibitors; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Real-Time Polymerase Chain Reaction; Repressor Proteins - antagonists & inhibitors; Repressor Proteins - genetics; Repressor Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Sequence Homology, Amino Acid; Tumor Cells, Cultured; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; Twist1; Wound Healing; Xenograft Model Antitumor Assays; epithelial-mesenchymal transition (EMT); cadherin-1 (CDH1) (epithelial cadherin) (E-cadherin); Prmt1; metastasis; N-cadherin; protein methylation; Twist1
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M114.636050

Protein arginine methyl transferase 1 (PRMT1) was shown to be up-regulated in cancers and important for cancer cell proliferation. However, the role of PRMT1 in lung cancer progression and metastasis remains incompletely understood. In the present study, we show that PRMT1 is an important regulator of epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion, which are essential processes during cancer progression, and metastasis. Additionally, we have identified Twist1, a basic helix-loop-helix transcription factor and a well-known E-cadherin repressor, as a novel PRMT1 substrate. Taken together, we show that PRMT1 is a novel regulator of EMT and arginine 34 (Arg-34) methylation of Twist1 as a unique “methyl arginine mark” for active E-cadherin repression. Therefore, targeting PRMT1-mediated Twist1 methylation might represent a novel strategy for developing new anti-invasive/anti-metastatic drugs. Moreover, methylated Twist1 (Arg-34), as such, could also emerge as a potential important biomarker for lung cancer. Background: PRMT1 is up-regulated in lung cancer. Results: PRMT1 is a novel regulator of EMT and Twist1 is a new PRMT1 substrate. Conclusion: PRMT1-methylation of Twist1 is required for active E-cadherin repression. Significance: Targeting PRMT1-mediated Twist1 methylation might represent a novel strategy for developing new anti-invasive/anti-metastatic drugs.