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HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis

机译:HOXB9,一种在乳腺癌中过表达的基因,可促进致瘤性和肺转移

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摘要

The mechanisms underlying tumoral secretion of signaling molecules into the microenvironment, which modulates tumor cell fate, angiogenesis, invasion, and metastasis, are not well understood. Aberrant expression of transcription factors, which has been implicated in the tumorigenesis of several types of cancers, may provide a mechanism that induces the expression of growth and angiogenic factors in tumors, leading to their local increase in the tumor microenvironment, favoring tumor progression. In this report, we demonstrate that the transcription factor HOX69 is overexpressed in breast carcinoma, where elevated expression correlates with high tumor grade. HOXB9 induces the expression of several angiogenic factors (VEGF, bFGF, IL-8, and ANGPTL-2), as well as ErbB (amphiregulin, epiregulin, and neuregulins) and TGF-β, which activate their respective pathways, leading to increased cell motility and acquisition of mesenchymal phenotypes. In vivo, HOXB9 promotes the formation of large, well-vascularized tumors that metastasize to the lung. Thus, deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.
机译:信号分子向微环境中肿瘤分泌的潜在机制尚不清楚,该机制调节肿瘤细胞的命运,血管生成,侵袭和转移。转录因子的异常表达已与几种类型的癌症的发生有关,它可能提供一种机制,诱导肿瘤中生长因子和血管生成因子的表达,从而导致它们在肿瘤微环境中的局部增加,有利于肿瘤的进展。在本报告中,我们证明了转录因子HOX69在乳腺癌中过表达,其中高表达与高肿瘤等级相关。 HOXB9诱导几种血管生成因子(VEGF,bFGF,IL-8和ANGPTL-2)以及ErbB(双调蛋白,上调蛋白和神经调节蛋白)和TGF-β的表达,它们激活各自的途径,导致细胞增多运动和间充质表型的获得。在体内,HOXB9促进转移到肺部的大血管化肿瘤的形成。因此,HOXB9的失调表达通过诱导几种改变肿瘤特异性细胞命运和肿瘤基质微环境的生长因子而促进了乳腺癌的进展和肺转移。

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  • 作者单位

    Department of Surgery, Hospital and Harvard Medical School, Charlestown, MA 02129 Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Department of Surgery, Hospital and Harvard Medical School, Charlestown, MA 02129 Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Department of Surgery, Hospital and Harvard Medical School, Charlestown, MA 02129 Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Department of Pathology, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Department of Surgery, Hospital and Harvard Medical School, Charlestown, MA 02129 Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263;

    Cell Biology and Stem Cells Unit, CIC bioGUNE, 48160 Derio, Bizkaia, Spain;

    Foster Biomedical Research Laboratory, Brandeis University, Waltham, MA 02254;

    Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129 Department of Pathology, Hospital and Harvard Medical School, Charlestown, MA 02129;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129;

    Department of Surgery, Hospital and Harvard Medical School, Charlestown, MA 02129 Center for Cancer Research, Hospital and Harvard Medical School, Charlestown, MA 02129;

  • 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

    breast cancer; ErbB; TGF-β; angiogenesis; epithelial to mesenchymal transition;

    机译:乳腺癌;ErbB;TGF-β;血管生成;上皮向间质转化;

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