外源AGR2在结直肠癌细胞中的功能和机制
Chao Zheng1, Yu Mao1, Jianping Ye1
1Department of General Surgery, The People's Hospital of Yuhuan, Taizhou, 317600, Zhejiang, China.
Heliyon
|April 1, 2024
概括
前梯度2 (AGR2) 通过AKT/β-catenin通路诱导上皮层-介质细胞过渡 (EMT) 促进结直肠癌 (CRC) 细胞生长和转移. 这一发现澄清了AGR2在CRC进展中的作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 前侧梯度2 (AGR2) 在各种癌症中过度表达,并与转移有关.
- 在结肠直肠癌 (CRC) 中AGR2的特定作用仍然在很大程度上未被定义.
研究的目的:
- 为了研究AGR2在结直肠癌中的表达和功能.
- 阐明AGR2-介导的CRC进展的潜在分子机制.
主要方法:
- 在CRC细胞系中使用GEPIA数据库和Western blot进行AGR2表达分析.
- 功能测试包括CCK-8,克隆形成,伤口愈合和Transwell测试,以评估细胞增殖,迁移和入侵.
- 西部斑点分析以确定与AKT/β-catenin信号通路和上皮-介质细胞过渡 (EMT) 相关的蛋白质表达.
主要成果:
- 与正常组织相比,CRC组织中的AGR2表达显著增加.
- 过度表达AGR2增强了CRC细胞的增殖,迁移和入侵.
- 在CRC细胞中,AGR2诱导EMT,由ZEB1,N-cadherin,Vimentin,Slug和Snail的表达增加和E-cadherin的减少证明.
- AGR2对AKT/β-catenin信号通路进行上调,包括p-AKT,p-GSK3β和β-catenin水平.
- 使用AGR2和AKT激动因子 (IGF-I) 的联合治疗进一步增强了CRC细胞的生长和入侵.
结论:
- AGR2显著促进结直肠癌细胞的增殖和转移.
- 在CRC细胞中,AGR2通过激活AKT/β-catenin信号通路来诱导EMT.
- 向AGR2可能是结直肠癌的潜在治疗策略.
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