|国家预印本平台
首页|三链核酸介导ErbB-2交联的细胞功能调控

三链核酸介导ErbB-2交联的细胞功能调控

rplex Nucleic Acid Mediated ErbB-2 Crosslinking for Regulation of Cell Function

中文摘要英文摘要

表皮生长因子受体2(ErbB-2)是乳腺癌、胃癌、结直肠癌、卵巢癌和膀胱癌肿瘤细胞膜上过表达的一个关键的致癌生物标志物。此外,ErbB-2常与ErbB家族其他成员发生同源二聚化或异源二聚化,导致与癌细胞生存和恶性表型相关的信号转导通路被激活,从而促进不受控制的细胞生长和诱导癌症发生。开发新的靶向ErbB-2受体降解的治疗方式具有重要研究意义。本文利用三链核酸对目标蛋白进行调控,设计了能够结合细胞膜上ErbB-2受体的三链核酸适体探针TrplexDNA,TrplexDNA可以对ErbB-2受体进行数量的调控,增强将ErbB-2受体转运到溶酶体中降解的能力,破坏ErbB-2的同源/异源二聚体,阻断下游信号通路的激活,抑制肿瘤细胞的增殖、生长和迁移。同时可以拉近细胞膜上ErbB-2受体的距离,使其发生受体交联效应,引起钙离子内流和Caspase活化,进一步增强细胞凋亡。

Epidermal growth factor receptor 2 (ErbB-2) is a key oncogenic biomarker overexpressed on the cell membranes of breast, gastric, colorectal, ovarian and bladder cancers. In addition, ErbB-2 often induces autodimerization or heterodimerization with other members of the ErbB family, leading to the activation of signal transduction pathways related to cancer cell survival and malignant phenotype, thereby promoting uncontrolled cell growth and inducing carcinogenesis. It is of great significance to develop new therapeutic methods targeting ErbB-2 receptor degradation. In this study, a three-stranded aptamer probe TrplexDNA binds to ErbB-2 receptors on cell membrane was designed to regulate the number of ErbB-2 receptors, enhance the ability of transporting ErbB-2 receptors to lysosomes for degradation, and destroy the homologous/heterologous dimer of ErbB-2. Inhibit the activation of downstream signaling pathways and inhibit the proliferation, growth and migration of tumor cells. TrplexDNA can also shorten the distance of ErbB-2 receptors on the cell membrane, resulting in receptor crosslinking effect, calcium influx and Caspase activation, and further enhance cell apoptosis.

薛倩、邹振

肿瘤学基础医学分子生物学

表皮生长因子受体2靶向蛋白降解溶酶体核酸适体细胞功能调控

Epidermal growth factor receptor 2Targeted protein degradationLysosomeNucleic acid aptamercell function regulation.

薛倩,邹振.三链核酸介导ErbB-2交联的细胞功能调控[EB/OL].(2022-04-29)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/202204-329.点此复制

评论