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

J Biol Chem. 2015 May 22;290(21):13479-89. doi: 10.1074/jbc.M114.636050. Epub 2015 Apr 6.

Abstract

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.

Keywords: N-cadherin; Prmt1; Twist1; cadherin-1 (CDH1) (epithelial cadherin) (E-cadherin); epithelial-mesenchymal transition (EMT); metastasis; protein methylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arginine / genetics
  • Blotting, Western
  • 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*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein-Arginine N-Methyltransferases / antagonists & inhibitors
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism
  • Wound Healing
  • Xenograft Model Antitumor Assays

Substances

  • Cadherins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Repressor Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Arginine
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases