論文 - 詳細
| RRC ID | 81851 |
|---|---|
| 著者 | Kakemura B, Igaki T. |
| タイトル | Blockade of Crk eliminates Yki/YAP-activated tumors via JNK-mediated apoptosis in Drosophila. |
| ジャーナル | Commun Biol |
| Abstract |
Selective elimination of cancer cells without causing deleterious effects on normal cells is an ideal anti-cancer strategy. Here, using Drosophila cancer model, we performed an in vivo RNAi screen for anti-cancer targets that selectively eliminate tumors without affecting normal tissue growth. In Drosophila imaginal epithelium, clones of cells expressing oncogenic Ras with simultaneous mutations in the cell polarity gene scribble (RasV12/scrib-/-) develop into malignant tumors. We found that knockdown of Crk, the Drosophila ortholog of human CRK (CT10 regulatory kinase) and CRKL (Crk-like) adapter proteins, significantly suppresses growth of RasV12/scrib-/- tumors by inducing c-Jun N-terminal kinase (JNK)-mediated apoptosis, while it does not affect growth of normal epithelium. Mechanistically, Crk inhibition blocks Yorkie (Yki)/YAP activity by impairing F-actin accumulation, an upstream event of Yki/YAP activation in tumors. Inhibition of Yki/YAP in tumors causes intracellular JNK signaling to be used for apoptosis induction. Given that molecules and signaling pathways identified in Drosophila are highly conserved and activated in human cancers, our findings would provide a novel, to the best of our knowledge, anti-cancer strategy against YAP-activated cancers. |
| 巻・号 | 7(1) |
| ページ | 1196 |
| 公開日 | 2024-9-28 |
| DOI | 10.1038/s42003-024-06897-w |
| PII | 10.1038/s42003-024-06897-w |
| PMID | 39341909 |
| PMC | PMC11438906 |
| MeSH | Animals Apoptosis* Drosophila / genetics Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism Neoplasms / genetics Neoplasms / metabolism Neoplasms / pathology Nuclear Proteins / genetics Nuclear Proteins / metabolism Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-crk / genetics Proto-Oncogene Proteins c-crk / metabolism Trans-Activators* / genetics Trans-Activators* / metabolism YAP-Signaling Proteins* / genetics YAP-Signaling Proteins* / metabolism |
| IF | 4.165 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | 4005R-2 |