PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer

Cancer Res. 2017 Sep 1;77(17):4613-4625. doi: 10.1158/0008-5472.CAN-17-0216. Epub 2017 Jun 27.


Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR.

Publication types

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

MeSH terms

  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Mice
  • Mice, Knockout
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Protein Biosynthesis*
  • Protein-Arginine N-Methyltransferases / physiology*
  • Proteomics
  • Retinoblastoma Protein / physiology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology*
  • Xenograft Model Antitumor Assays


  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Prmt1 protein, mouse
  • Protein-Arginine N-Methyltransferases