| First Author | Rominger MC | Year | 2025 |
| Journal | Cell Rep | Volume | 44 |
| Issue | 10 | Pages | 116185 |
| PubMed ID | 41004338 | Mgi Jnum | J:373435 |
| Mgi Id | MGI:8253817 | Doi | 10.1016/j.celrep.2025.116185 |
| Citation | Rominger MC, et al. (2025) Mutant RIT1 cooperates with YAP to drive an EMT-like lung cancer state. Cell Rep 44(10):116185 |
| abstractText | Mutations in "Ras-like in all tissues" (RIT1) occur in up to 2% of lung adenocarcinomas and are mutually exclusive with KRAS and EGFR mutations, suggesting that RIT1 may act as a non-canonical driver oncogene in lung cancer. However, the lack of a RIT1-mutant lung cancer model has hindered the development and testing of RIT1-targeted therapeutics. Here, we report a mouse model with conditional regulation of the cancer-associated RIT1(M90I) variant. We show that autochthonous expression of RIT1(M90I) and combined inactivation of Nf2 and p53 drives an aggressive lung cancer with 100% penetrance and short latency. Oncogenic cooperation between RIT1(M90I) and p53/Nf2 loss is driven by synergistic activation of AP-1 transcription factors and can be reversed by the combined inhibition of MEK and TEAD. These data identify YAP/TEAD as a mediator of RIT1's oncogenic capability and nominate TEAD as a potential drug target in RIT1-mutant lung cancer. |
