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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A 'latent niche' mechanism for tumor initiation
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A 'latent niche' mechanism for tumor initiation

机译：肿瘤启动的“潜在利基”机制

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摘要

Stem cells, their niches, and their relationship to cancer are under intense investigation. Because tumors and metastases acquire self-renewing capacity, mechanisms for their establishment may involve cell-cell interactions similar to those between stem cells and stem cell niches. On the basis of our studies in Caenorhabditis elegans, we introduce the concept of a "latent niche" as a differentiated cell type that does not normally contact stem cells nor act as a niche but that can, under certain conditions, promote the ectopic self-renewal, proliferation, or survival of competent cells that it inappropriately contacts. Here, we show that ectopic germ-line stem cell proliferation in C elegans is driven by a latent niche mechanism and that the molecular basis for this mechanism is inappropriate Notch activation. Furthermore, we show that continuous Notch signaling is required to maintain ectopic germ-line proliferation. We highlight the latent niche concept by distinguishing it from a normal stem cell niche, a premetastatic niche and an ectopic niche. One of the important distinguishing features of this mechanism for tumor initiation is that it could operate in the absence of genetic changes to the tumor cell or the tumor-promoting cell. We propose that a latent niche mechanism may underlie tumorigenesis and metastasis in humans.
机译：干细胞，其壁ni及其与癌症的关系正在深入研究中。由于肿瘤和转移瘤具有自我更新的能力，因此其建立机制可能涉及类似于干细胞和干细胞生态位之间的细胞-细胞相互作用。在我们对秀丽隐杆线虫的研究的基础上，我们引入“潜伏生态位”的概念，这种分化的细胞类型通常不接触干细胞也不充当生态位，但在某些条件下可以促进异位自我分化。不适当地接触的感受态细胞的更新，增殖或存活。在这里，我们表明秀丽隐杆线虫异位生殖干细胞增殖是由潜在的利基机制驱动的，并且该机制的分子基础是不适当的Notch激活。此外，我们表明需要连续的Notch信号来维持异位种系的增殖。我们通过将其与正常干细胞生态位，转移前生态位和异位生态位区分开来突出潜在生态位概念。该肿瘤引发机制的重要区别特征之一是它可以在没有肿瘤细胞或肿瘤促进细胞遗传改变的情况下起作用。我们建议潜在的利基机制可能是人类肿瘤发生和转移的基础。

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  • 作者

    Marie McGovern; Roumen Voutev; John Maciejowski; Ann K. Corsi; E. Jane Albert Hubbard;

  • 作者单位

    Developmental Genetics Program, Helen and Martin Kimmel Center for Stem Cell Biology, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, NY 10016;

    Developmental Genetics Program, Helen and Martin Kimmel Center for Stem Cell Biology, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, NY 10016 Department of Biology, New York University, 100 Washington Square East, New York, NY 10003;

    Department of Biology, New York University, 100 Washington Square East, New York, NY 10003;

    Department of Biology, The Catholic University of America, Washington, DC 20064;

    Developmental Genetics Program, Helen and Martin Kimmel Center for Stem Cell Biology, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, NY 10016;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    caenorhabditis elegans; delta/serrate/LAG-2; notch; stem cell; pro phenotype;

    机译：秀丽隐杆线虫;delta / serrate / LAG-2;缺口;干细胞;表型;

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