亚斯巴酸信号通过替代翻译驱动肺转移
Ginevra Doglioni1,2, Juan Fernández-García1,2, Sebastian Igelmann1,2
1Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium.
Nature
|January 1, 2025
概括
通过激活癌细胞信号, 这种氨基酸促进转化程序, 增加乳腺癌在肺部的攻击性.
科学领域:
- 癌症学
- 细胞生物学
- 生物化学
背景情况:
- 肺部转移在癌症患者中很常见,受肺部环境和瘤分泌因素的影响.
- 营养素在转移前形成和癌细胞攻击性中的作用在很大程度上仍未确定.
- 了解营养驱动机制对于向转移性疾病至关重要.
研究的目的:
- 研究肺部微环境中的营养物质如何促进癌细胞的攻击性.
- 确定特定的分子途径,将肺部营养物质与转移增强.
- 确定阿斯巴达酸是否影响肺转移的攻击性特征.
主要方法:
- 分析患有乳腺癌的患者和小鼠的肺间液中的酸盐度.
- 研究癌细胞中N-甲基-D-酸盐受体的激活和下游信号.
- 评估脱氧素酶 (DOHH) 和低化在癌细胞转化中的作用.
- 检查TGFβ信号通路和肺转移中的原合成.
- 在人肺转移中检测关键蛋白标志物.
主要成果:
- 乳腺癌患者和小鼠的肺间液中发现了高酸盐水平.
- 细胞外阿斯巴酸激活癌细胞中的N-甲基-D-阿斯巴酸受体,通过CREB对DOHH进行上调.
- 这对eIF5A活动和积极的转化计划至关重要.
- TGFβ信号作为一个中心枢纽,促进肺部扩散的癌细胞中的原合成.
- 在人类乳腺癌肺转移中确定了分子机制.
结论:
- 肺部酸盐在肺部微环境中充当细胞外信号分子.
- 亚斯巴酸会引发一连串导致肺转移的增加.
- 这一途径涉及N-甲基-D-酸盐受体激活,DOHH和TGFβ信号传递.
- 针对这种由酸盐驱动的机制可以为肺转移提供新的治疗策略.
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