通过EGFR/Akt/mTOR信号级联和动态促进结直肠癌转移
Mayu Sun1, Zheshun Jiang1, Pengfei Gu1
1State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The Science of the total environment
|July 26, 2023
概括
慢性低剂量暴露通过改变细胞结节和激活表皮生长因子受体 (EGFR) 信号,促进结直肠癌 (CRC) 转移. 这种独特的EGFR激活增强了CRC细胞入侵和肝脏转移.
科学领域:
- 环境毒理学环境毒理学
- 癌症生物学 癌症生物学
- 分子信号传递是分子信号传递.
背景情况:
- (Cd) 是一种有毒的重金属,具有重要的食物传播暴露途径.
- 肠道易受Cd毒性影响,但其对结直肠癌 (CRC) 的慢性影响尚不清楚.
- 了解Cd在CRC病原发生中的作用对于公共卫生至关重要.
研究的目的:
- 研究慢性低剂量暴露对结肠直肠癌 (CRC) 发展的长期影响.
- 阐明潜在的分子机制,特别关注关键的信号通路.
- 确定表皮生长因子受体 (EGFR) 信号在Cd诱导的CRC转移中的作用.
主要方法:
- 使用CRC细胞和小鼠模型进行体外和体外研究.
- 对细胞结相关的基因表达和细胞移动性标记物的分析.
- 研究表皮生长因子受体 (EGFR) 信号通路,包括ERK和Akt/mTOR级联.
- 药理上阻断EGFR以评估其在转移中的作用.
主要成果:
- 慢性低剂量Cd暴露增强了CRC细胞入侵和转移在体外和体内.
- 暴露在Cd下调细胞结基因和增加细胞移动性的分子.
- Cd以非正规的方式激活了EGFR信号,诱导了持续的信号和Akt/mTOR激活,与EGF不同.
- EGFR阻断显著降低了Cd诱导的CRC细胞的肝转移.
结论:
- 环境中的暴露通过独特的EGFR信号动态促进结直肠癌转移.
- Cd的非正规EGFR激活优先提高转移能力而不是细胞生长.
- 向EGFR信号可能提供针对Cd诱导的CRC转移的治疗策略.
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