...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature cancer. >AP0BEC3A drives deaminase domain-independent chromosomal instability to promote pancreatic cancer metastasis
【24h】

AP0BEC3A drives deaminase domain-independent chromosomal instability to promote pancreatic cancer metastasis

机译：AP0BEC3A驱动器脱氨酶特定领域染色体不稳定,促进胰腺癌症转移

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

Despite efforts in understanding its underlying mechanisms, the etiology of chromosomal instability (CIN) remains unclear for many tumor types. Here, we identify CIN initiation as a previously undescribed function for APOBEC3A (A3A), a cytidine deaminase upregulated across cancer types. Using genetic mouse models of pancreatic ductal adenocarcinoma (PDA) and genomics analyses in human tumor cells we show that A3A-induced CIN leads to aggressive tumors characterized by enhanced early dissemination and metastasis in a STING-dependent manner and independently of the canonical deaminase functions of A3A. We show that A3A upregulation recapitulates numerous copy number alterations commonly observed in patients with PDA, including co-deletions in DNA repair pathway genes, which in turn render these tumors susceptible to poly (ADP-ribose) polymerase inhibition. Overall, our results demonstrate that A3A plays an unexpected role in PDA as a specific driver of CIN, with significant effects on disease progression and treatment.
机译：尽管努力理解它的底层机制,染色体的病因不稳定对许多肿瘤(CIN)尚不清楚类型。APOBEC3A之前从未描述函数(A3A)、胞嘧啶核苷脱氨酶调节癌症类型。胰腺导管腺癌(PDA)和在人类肿瘤细胞基因组学分析我们节目A3A-induced CIN导致侵略性的肿瘤特点是早期传播和增强STING-dependent方式和转移独立的规范脱氨酶A3A的函数。概括大量拷贝数变化通常观察到PDA患者,包括co-deletions在DNA修复途径的基因,依次呈现这些肿瘤容易聚(ADP-ribose)聚合酶抑制。结果表明,A3A扮演一个意想不到的作用在PDA CIN的特定驱动程序,对疾病进展和显著的影响治疗。

著录项

相似文献

  • 外文文献
  • 中文文献
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