GSTDTAP  > 气候变化
DOI10.1111/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
ISSN0028-0836
EISSN1476-4687
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
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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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