論文 - 詳細
| RRC ID | 76436 |
|---|---|
| 著者 | Oka T, Higa T, Sugahara O, Koga D, Nakayama S, Nakayama KI. |
| タイトル | Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence after Chemotherapy of Intestinal Tumors. |
| ジャーナル | Cancer Res |
| Abstract |
UNLABELLED:Quiescent cancer stem cells (CSC) are resistant to conventional anticancer treatments and have been shown to contribute to disease relapse after therapy in some cancer types. The identification and characterization of quiescent CSCs could facilitate the development of strategies to target this cell population and block recurrence. Here, we established a syngeneic orthotopic transplantation model in mice based on intestinal cancer organoids to profile quiescent CSCs. Single-cell transcriptomic analysis of the primary tumors formed in vivo revealed that conventional Lgr5high intestinal CSCs comprise both actively and slowly cycling subpopulations, the latter of which specifically expresses the cyclin-dependent kinase inhibitor p57. Tumorigenicity assays and lineage tracing experiments showed that the quiescent p57+ CSCs contribute in only a limited manner to steady-state tumor growth but they are chemotherapy resistant and drive posttherapeutic cancer recurrence. Ablation of p57+ CSCs suppressed intestinal tumor regrowth after chemotherapy. Together, these results shed light on the heterogeneity of intestinal CSCs and reveal p57+ CSCs as a promising therapeutic target for malignant intestinal cancer. SIGNIFICANCE:A quiescent p57+ subpopulation of intestinal CSCs is resistant to chemotherapy and can be targeted to effectively suppress the recurrence of intestinal cancer. |
| 巻・号 | 83(9) |
| ページ | 1393-1409 |
| 公開日 | 2023-5-2 |
| DOI | 10.1158/0008-5472.CAN-22-2578 |
| PII | 718503 |
| PMID | 36880956 |
| MeSH | Animals Cell Division Cyclin-Dependent Kinase Inhibitor p57 Intestinal Neoplasms* / pathology Mice Neoplasm Recurrence, Local* / pathology Neoplastic Stem Cells / pathology |
| IF | 9.727 |
| リソース情報 | |
| 遺伝子材料 | pcDNA3 Venus-Akaluc (RDB15781) |