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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
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Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation

机译:低氧诱导因子1是乳腺癌转移性小生境形成的主要调控因子

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摘要

Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIM) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b~+ BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression.
机译:原发性肿瘤通过引导骨髓源性细胞(BMDC)在癌细胞到达之前在肺中定植来促进转移。在这里,我们证明低氧诱导因子1(HIM)是通过诱导赖氨酰氧化酶(LOX)家族的多个成员(包括LOX,LOX样2和LOX样4)诱导乳腺癌转移性生态位形成的关键调节剂。 ,它在BMDC募集之前催化肺中的胶原蛋白交联。在任何个体乳腺癌中仅表达了LOX家族成员的一个子集,但在每种情况下均需表达HIF-1。敲低HIF-1或低氧诱导的LOX家族成员可减少原位移植人乳腺癌细胞后胶原交联,CD11b〜+ BMDC募集以及小鼠肺中的转移形成。在乳腺癌进展过程中,转移性小生境的形成是HIF-1依赖性事件。

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  • 作者单位

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218;

    State Key Laboratory for Liver Research, Li Ka shing Faculty of Medicine, University of Hong Kong, Hong Kong ,Department of Pathology, Li Ka shing Faculty of Medicine, University of Hong Kong, Hong Kong;

    Department of Pathology, Li Ka shing Faculty of Medicine, University of Hong Kong, Hong Kong;

    State Key Laboratory for Liver Research, Li Ka shing Faculty of Medicine, University of Hong Kong, Hong Kong ,Department of Pathology, Li Ka shing Faculty of Medicine, University of Hong Kong, Hong Kong;

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218;

    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;

  • 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

    extracellular matrix; lung metastasis;

    机译:细胞外基质肺转移;

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