• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy
【24h】

A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy

机译：缓慢循环的LGR5肿瘤种群介导治疗后基底细胞癌复发

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Basal cell carcinoma (BCC) is the most frequent cancer in humans and results from constitutive activation of the Hedgehog pathway(1). Several Smoothened inhibitors are used to treat Hedgehog-mediated malignancies, including BCC and medulloblastoma(2). Vismodegib, a Smoothened inhibitor, leads to BCC shrinkage in the majority of patients with BCC3, but the mechanism by which it mediates BCC regression is unknown. Here we used two genetically engineered mouse models of BCC4 to investigate the mechanisms by which inhibition of Smoothened mediates tumour regression. We found that vismodegib mediates BCC regression by inhibiting a hair follicle-like fate and promoting the differentiation of tumour cells. However, a small population of tumour cells persists and is responsible for tumour relapse following treatment discontinuation, mimicking the situation found in humans(5). In both mouse and human BCC, this persisting, slow-cycling tumour population expresses LGR5 and is characterized by active Wnt signalling. Combining Lgr5 lineage ablation or inhibition of Wnt signalling with vismodegib treatment leads to eradication of BCC. Our results show that vismodegib induces tumour regression by promoting tumour differentiation, and demonstrates that the synergy between Wnt and Smoothened inhibitors is a clinically relevant strategy for overcoming tumour relapse in BCC.
机译：基底细胞癌（BCC）是人类中最常见的癌症，它是由Hedgehog途径的组成型激活引起的（1）。几种平滑化抑制剂可用于治疗刺猬介导的恶性肿瘤，包括BCC和髓母细胞瘤（2）。 Vismodegib是一种平滑化的抑制剂，可导致大多数BCC3患者的BCC缩小，但其介导BCC退化的机制尚不清楚。在这里，我们使用BCC4的两个基因工程小鼠模型来研究抑制平滑化介导肿瘤消退的机制。我们发现，vismodegib通过抑制毛囊样命运并促进肿瘤细胞的分化来介导BCC消退。但是，仍然存在一小部分肿瘤细胞，这是治疗中断后肿瘤复发的原因，与人类的情况相似（5）。在小鼠和人的BCC中，这种持续的，缓慢循环的肿瘤群体表达LGR5，其特征在于活跃的Wnt信号传导。 Lgr5沿袭消融或Wnt信号抑制与vismodegib治疗相结合可根除BCC。我们的结果表明，vismodegib通过促进肿瘤分化来诱导肿瘤消退，并证明Wnt和Smoothened抑制剂之间的协同作用是克服BCC肿瘤复发的临床相关策略。

著录项

  • 来源
    《Nature》 |2018年第7727期|434-438|共5页
  • 作者

    Sanchez-Danes Adriana; Larsimont Jean-Christophe; Liagre Melanie; Munoz-Couselo Eva; Lapouge Gaelle; Brisebarre Audrey; Dubois Christine; Suppa Mariano; Sukumaran Vijayakumar; del Marmol Veronique; Tabernero Josep; Blanpain Cedric;

  • 作者单位

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Barcelona, Spain;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Libre Bruxelles, Erasme Hosp, Dept Dermatol, Brussels, Belgium;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

    Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Barcelona, Spain;

    Univ Libre Bruxelles, Lab Stem Cells & Canc, Brussels, Belgium;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号