| First Author | Carugo A | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 2 | Pages | 204-220.e9 |
| PubMed ID | 30753823 | Mgi Jnum | J:271233 |
| Mgi Id | MGI:6279490 | Doi | 10.1016/j.ccell.2019.01.006 |
| Citation | Carugo A, et al. (2019) p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors. Cancer Cell 35(2):204-220.e9 |
| abstractText | Alterations in chromatin remodeling genes have been increasingly implicated in human oncogenesis. Specifically, the biallelic inactivation of the SWI/SNF subunit SMARCB1 results in the emergence of extremely aggressive pediatric malignancies. Here, we developed embryonic mosaic mouse models of malignant rhabdoid tumors (MRTs) that faithfully recapitulate the clinical-pathological features of the human disease. We demonstrated that SMARCB1-deficient malignancies exhibit dramatic activation of the unfolded protein response (UPR) and ER stress response via a genetically intact MYC-p19(ARF)-p53 axis. As a consequence, these tumors display an exquisite sensitivity to agents inducing proteotoxic stress and inhibition of the autophagic machinery. In conclusion, our findings provide a rationale for drug repositioning trials investigating combinations of agents targeting the UPR and autophagy in SMARCB1-deficient MRTs. |
