• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Cancer Stem Cell-Induced Vascularization of Skin Cancer Tumors is Driven by Novel Signaling Mechanism Specific to VEGF-A/NRP-1 Interaction
【24h】

Cancer Stem Cell-Induced Vascularization of Skin Cancer Tumors is Driven by Novel Signaling Mechanism Specific to VEGF-A/NRP-1 Interaction

机译：癌干细胞诱导的皮肤癌肿瘤血管化是由新型信号传导机制驱动的，该机制专门针对VEGF-A / NRP-1相互作用

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

Epidermal squamous cell carcinoma is among the most common cancers. These tumors are comprised of phenotypically diverse populations of cells that display varying potential for proliferation and differentiation. An important goal is identifying cells from this population that drive tumor formation, in order to therapeutically target and eliminate this population of cells. To enrich for tumor-forming cells, cancer cells were grown as spheroids in non-attached conditions. Detailed analysis reveals that spheroid-selected cultures are highly enriched for expression of epidermal stem cell and embryonic stem cell markers, including ALDH1, keratin 15, CD200, and keratin 19. This limited subpopulation of epidermal cancer stem cells (ECS cells), in squamous cell carcinoma, form rapidly growing, invasive and highly vascularized tumors, as compared with non stem cancer cells. We show that ECS cell-produced vascular endothelial growth factor (VEGF)-A is required for the maintenance of this phenotype, as knockdown of VEGF-A gene expression or treatment with VEGF-A inactivating antibody reduces these responses. Surprisingly, the classical mechanism of VEGF-A action via interaction with VEGF receptors does not mediate these events, as these cells lack VEGFR1 and VEGFR2. Instead, VEGF-A acts via the Neuropilin-1 (NRP-1) co-receptor to trigger intracellular events leading to ECS cell survival and formation of aggressive, invasive and highly vascularized tumors. We further identify a novel signaling cascade downstream of this VEGF-A/NRP-1 interaction that shows NRP-1 forms a complex with GIPC1 and alpha6/b4-integrin to activate FAK/Src signaling which leads to stabilization of a YAP1/DeltaNp63alpha to enhance ECS cell survival, invasion and angiogenesis.
机译：表皮鳞状细胞癌是最常见的癌症。这些肿瘤由表型多样的细胞群组成，这些细胞群表现出不同的增殖和分化潜能。一个重要的目标是从该群体中鉴定出驱动肿瘤形成的细胞，以便治疗性靶向并消除该细胞群体。为了富集形成肿瘤的细胞，癌细胞在非附着条件下以球状体的形式生长。详细分析显示，球状细胞选择培养物高度丰富，用于表皮干细胞和胚胎干细胞标志物的表达，包括ALDH1，角蛋白15，CD200和角蛋白19。鳞状上皮癌干细胞（ECS细胞）的这种有限的亚群与非干癌细胞相比，细胞癌会形成快速生长，侵袭性和高度血管化的肿瘤。我们显示，ECS细胞产生的血管内皮生长因子（VEGF）-A是维持该表型所必需的，因为敲低VEGF-A基因表达或用VEGF-A灭活抗体治疗可减少这些反应。出乎意料的是，通过与VEGF受体相互作用，VEGF-A作用的经典机制并未介导这些事件，因为这些细胞缺乏VEGFR1和VEGFR2。取而代之的是，VEGF-A通过Neuropilin-1（NRP-1）共受体起作用，触发细胞内事件，导致ECS细胞存活并形成侵袭性，侵袭性和高度血管化的肿瘤。我们进一步确定了这种VEGF-A / NRP-1相互作用下游的新型信号传导级联，显示NRP-1与GIPC1和alpha6 / b4-整联蛋白形成复合物以激活FAK / Src信号传导，从而导致YAP1 / DeltaNp63alpha的稳定化​​。增强ECS细胞存活，侵袭和血管生成。

著录项

  • 作者

    Grun, Daniel J.B.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Biochemistry.;Oncology.
  • 学位 Ph.D.
  • 年度 2017
  • 页码 134 p.
  • 总页数 134
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

  • 入库时间 2022-08-17 11:54:28

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