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DOI | 10.1111/gcb.13385 |
A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer | |
de Sousa e Melo, Felipe1; Kurtova, Antonina V.1; Harnoss, Jonathan M.2; Kljavin, Noelyn1; Hoeck, Joerg D.1; Hung, Jeffrey3; Anderson, Jeffrey Eastham3; Storm, Elaine E.1; Modrusan, Zora4; Koeppen, Hartmut3; Dijkgraaf, Gerrit J. P.1; Piskol, Robert5; de Sauvage, Frederic J.1 | |
2017-03-30 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 543期号:7647页码:676-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Cancer stem cells (CSCs) have been hypothesized to represent the driving force behind tumour progression and metastasis, making them attractive cancer targets. However, conclusive experimental evidence for their functional relevance is still lacking for most malignancies. Here we show that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal CSCs in mouse tumours engineered to recapitulate the clinical progression of human colorectal cancer. We demonstrate that selective Lgr5(+) cell ablation restricts primary tumour growth, but does not result in tumour regression. Instead, tumours are maintained by proliferative Lgr5-cells that continuously attempt to replenish the Lgr5+ CSC pool, leading to rapid re-initiation of tumour growth upon treatment cessation. Notably, CSCs are critical for the formation and maintenance of liver metastasis derived from colorectal cancers. Together, our data highlight distinct CSC dependencies for primary versus metastasic tumour growth, and suggest that targeting CSCs may represent a therapeutic opportunity for managing metastatic disease. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000397619700047 |
WOS关键词 | COLORECTAL-CANCER ; INTESTINAL REGENERATION ; CHROMOSOMAL INSTABILITY ; INITIATING CELLS ; SEQUENCING DATA ; MODEL ; POPULATION ; EXPRESSION ; IDENTIFICATION ; TUMORIGENESIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/17193 |
专题 | 气候变化 资源环境科学 |
作者单位 | 1.Genentech Inc, Mol Oncol, 1 DNA Way, San Francisco, CA 94080 USA; 2.Genentech Inc, Canc Immunol, 1 DNA Way, San Francisco, CA 94080 USA; 3.Genentech Inc, Res Pathol, 1 DNA Way, San Francisco, CA 94080 USA; 4.Genentech Inc, Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA; 5.Genentech Inc, Bioinformat & Computat Biol, 1 DNA Way, San Francisco, CA 94080 USA |
推荐引用方式 GB/T 7714 | de Sousa e Melo, Felipe,Kurtova, Antonina V.,Harnoss, Jonathan M.,et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer[J]. NATURE,2017,543(7647):676-+. |
APA | de Sousa e Melo, Felipe.,Kurtova, Antonina V..,Harnoss, Jonathan M..,Kljavin, Noelyn.,Hoeck, Joerg D..,...&de Sauvage, Frederic J..(2017).A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer.NATURE,543(7647),676-+. |
MLA | de Sousa e Melo, Felipe,et al."A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer".NATURE 543.7647(2017):676-+. |
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