| First Author | Hsu JH | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 17 | Pages | 4613-4625 |
| PubMed ID | 28655788 | Mgi Jnum | J:245660 |
| Mgi Id | MGI:5916042 | Doi | 10.1158/0008-5472.CAN-17-0216 |
| Citation | Hsu JH, et al. (2017) PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer. Cancer Res 77(17):4613-4625 |
| abstractText | 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. (c)2017 AACR. |
