Amyloid ┑ and Tumorigenesis: Amyloid ┑-Induced Telomere Dysfunction in Tumor Cells,CCS Chemistry

当前位置： X-MOL 学术 › CCS Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Amyloid ┑ and Tumorigenesis: Amyloid ┑-Induced Telomere Dysfunction in Tumor Cells
CCS Chemistry ( IF 9.4 ) Pub Date : 2019-08-07 , DOI: 10.31635/ccschem.019.20180034
Hongshuang Qin ₁ , Jiasi Wang _{1,

2} , Jinsong Ren ₁ , Xiaogang Qu ₁

Affiliation

The biological functions of amyloid ┑ (A┑) peptides have received much attention, playing a central role in the pathogenesis of Alzheimer’s disease (AD). Recent studies have demonstrated that AD is associated with cancer. However, it is still unknown if there is a correlation between A┑ and cancer. In this report, we investigated the effect of A┑42, the more fibrillogenic form of A┑ peptides, on telomere and telomerase sustenance in tumor cells. Telomere maintenance and telomerase reactivation are the early events in carcinogenesis and play essential roles for cell immortality and tumor initiation. Our study found that janus-faced A┑42 could target telomeres and induce classical telomere dysfunction, including telomere DNA damage, telomere uncapping, chromosome fusion, and telomere shortening. Furthermore, A┑42 could induce telomerase reverse transcriptase (TERT) downregulation, TERT translocation, inhibition of telomerase activity, as well as cell senescence and apoptosis. To our knowledge, this is the first report that provides a link between janus-faced A┑ and tumorigenesis. Our work would help in gaining a better understanding of the correlation between AD and cancer.

中文翻译：

淀粉样┑和肿瘤发生：淀粉样loid诱导的肿瘤细胞端粒功能障碍。

淀粉样蛋白┑（A┑）肽的生物学功能备受关注，在阿尔茨海默氏病（AD）的发病机理中起着核心作用。最近的研究表明，AD与癌症有关。但是，仍不清楚A┑与癌症之间是否存在相关性。在这份报告中，我们研究了A┑42（A┑肽的更多原纤维形成形式）对肿瘤细胞端粒和端粒酶维持的影响。端粒的维持和端粒酶的激活是癌变的早期事件，对细胞永生和肿瘤的发生起着至关重要的作用。我们的研究发现，面对贾努斯的A┑42可以靶向端粒并诱导经典的端粒功能障碍，包括端粒DNA损伤，端粒解盖，染色体融合和端粒缩短。此外，A┑42可诱导端粒酶逆转录酶（TERT）下调，TERT易位，抑制端粒酶活性以及细胞衰老和凋亡。据我们所知，这是第一篇报道了在子表面的A┑与肿瘤发生之间的联系。我们的工作将有助于更好地了解AD与癌症之间的相关性。

更新日期：2020-06-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文