論文 - 詳細
| RRC ID | 86161 |
|---|---|
| 著者 | Rominger MC, O'Brien S, Gupta S, Moorthi S, McSharry M, Kamlapurkar S, Lowe AR, Waldum A, Lo A, Duke F, Wu F, Headley MB, Cromwell E, Glabman R, Koehne A, Berger AH. |
| タイトル | Mutant RIT1 cooperates with YAP to drive an EMT-like lung cancer state. |
| ジャーナル | Cell Rep |
| Abstract |
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 RIT1M90I variant. We show that autochthonous expression of RIT1M90I and combined inactivation of Nf2 and p53 drives an aggressive lung cancer with 100% penetrance and short latency. Oncogenic cooperation between RIT1M90I 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. |
| 巻・号 | 44(10) |
| ページ | 116185 |
| 公開日 | 2025-10-28 |
| DOI | 10.1016/j.celrep.2025.116185 |
| PII | S2211-1247(25)00956-8 |
| PMID | 41004338 |
| MeSH | Adaptor Proteins, Signal Transducing* / genetics Adaptor Proteins, Signal Transducing* / metabolism Animals Cell Cycle Proteins Humans Lung Neoplasms* / genetics Lung Neoplasms* / metabolism Lung Neoplasms* / pathology Mice Mutation* / genetics Phosphoproteins* / metabolism Transcription Factors* / genetics Transcription Factors* / metabolism Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism YAP-Signaling Proteins ras Proteins* / genetics ras Proteins* / metabolism |
| IF | 8.109 |
| リソース情報 | |
| 実験動物マウス | RBRC02344 |