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Angiomotin-like 1 plays a tumor-promoting role in glioma by enhancing the activation of YAP1 signaling
Environmental Toxicology ( IF 4.4 ) Pub Date : 2021-09-04 , DOI: 10.1002/tox.23363
Gang Xu 1 , Zhiyuan Seng 1 , Ming Zhang 1 , Jianqiang Qu 1
Affiliation  

Angiomotin-like 1 (AMOTL1) is reportedly a pivotal tumor-associated protein that is strongly associated with the tumorigenesis of multiple malignant tumors. However, the issue of whether AMOTL1 plays a role in the tumorigenesis of glioma remains unclear. The aim of this work was to explore the possible relationship between AMOTL1 and glioma progression. Results demonstrated that high levels of AMOTL1 in glioma tissues were associated with a reduced survival rate in patients with glioma. Cellular functional assays revealed that silencing of AMOTL1 in glioma cell lines substantially decreased cell proliferation and invasion and increased cell apoptosis. Further investigation revealed that silencing of AMOTL1 inhibited the activation of yes-associated protein 1 (YAP1) and decreased the expression of YAP1 target genes. Reactivation of YAP1 reversed AMOTL1-silencing-induced antitumor effects, whereas inhibition of YAP1 abolished AMOTL1-overexpression-induced tumor-promoting effects in glioma cells. Silencing of AMOTL1 also retarded the growth of glioma cell-derived xenograft tumors in vivo. In conclusion, these findings suggested that AMOTL1 may exert a tumor-promoting function in glioma by enhancing the activation of YAP1 signaling. This work suggested AMOTL1 as a potential target for the development of antiglioma therapy.

中文翻译:

血管动蛋白样 1 通过增强 YAP1 信号的激活在胶质瘤中发挥促癌作用

据报道,血管动蛋白样 1 (AMOTL1) 是一种关键的肿瘤相关蛋白,与多种恶性肿瘤的肿瘤发生密切相关。然而,AMOTL1 是否在胶质瘤的肿瘤发生中起作用的问题仍不清楚。这项工作的目的是探索 AMOTL1 与神经胶质瘤进展之间的可能关系。结果表明,胶质瘤组织中高水平的 AMOTL1 与胶质瘤患者的存活率降低有关。细胞功能分析表明,胶质瘤细胞系中 AMOTL1 的沉默显着降低了细胞增殖和侵袭并增加了细胞凋亡。进一步的研究表明,AMOTL1 的沉默抑制了 yes 相关蛋白 1(YAP1)的激活并降低了 YAP1 靶基因的表达。YAP1 的重新激活逆转了 AMOTL1 沉默诱导的抗肿瘤作用,而 YAP1 的抑制消除了胶质瘤细胞中 AMOTL1 过表达诱导的肿瘤促进作用。AMOTL1 的沉默也延缓了体内胶质瘤细胞衍生的异种移植肿瘤的生长。总之,这些发现表明 AMOTL1 可能通过增强 YAP1 信号的激活在胶质瘤中发挥促癌作用。这项工作表明 AMOTL1 是开发抗神经胶质瘤治疗的潜在靶点。这些发现表明 AMOTL1 可能通过增强 YAP1 信号的激活在胶质瘤中发挥促癌作用。这项工作表明 AMOTL1 是开发抗神经胶质瘤治疗的潜在靶点。这些发现表明 AMOTL1 可能通过增强 YAP1 信号的激活在胶质瘤中发挥促癌作用。这项工作表明 AMOTL1 是开发抗神经胶质瘤治疗的潜在靶点。
更新日期:2021-11-03
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