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铜代谢失调与表皮-介质细胞过渡有关:一项针对结肠直肠癌患者的试点研究

Rosanna Squitti^1,2, Vincenzo Tondolo^3,4, Amit Pal⁵

¹Department of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina-Gemelli Isola, 00186, Rome, Italy. rosanna.squitti@fbf-isola.it.

Biological trace element research

|November 18, 2024

概括

结直肠癌的进展与铜不平衡有关,影响细胞通过表皮细胞转移到介质细胞转移 (EMT) 传播. 这项研究揭示了铜的失调.

科学领域:

分子生物学分子生物学
癌症研究癌症研究
代谢学代谢学代谢学

背景情况:

大肠直肠癌 (CRC) 是癌症死亡的主要原因,通常是由转移引起的.
铜对于CRC的扩散和攻击性至关重要,它调节了诸如上皮细胞转化为介质细胞转化 (EMT) 等关键信号通路.
基因表达分析涉及铜代谢基因,如APP和SOD1,在CRC.

研究的目的:

调查铜调和结直肠癌进展之间的相关性.
探索铜在CRC中介导EMT中的作用.
确定参与铜代谢的特定基因和蛋白质,以及它们与CRC和EMT的关联.

主要方法:

系统生物学分析以确定CRC和铜代谢中常见的基因.
对CRC组织和血清中铜含量的定量分析.
在CRC组织中测量mRNA和关键基因 (APP,CTR1,LOXL2,纤维菌素,维门丁,温库林,CDH1,SOD1,CCS) 的蛋白质水平.
相关性分析以确定分子标记物之间的相互连接.

主要成果:

在CRC患者中观察到APP基因/蛋白质的升调和血清铜水平的增加.
CRC组织显示铜水平降低,CTR1mRNA降低,EMT标记物水平变化 (纤维连结素增加,维丁/素减少).
在素和CCS/APP之间,以及在APPmRNA和CDH1/SOD1mRNA之间发现了显著的相关性,将铜不平衡与EMT联系起来.

结论:

细胞铜不平衡和结直肠癌进展之间存在相关性,由EMT调解.
这些发现为进一步研究铜失调动力学及其在CRC期间EMT调制中的作用提供了基础.
铜代谢代表了管理CRC转移的潜在治疗标.

关键词:

癌症的进展情况.结肠直肠癌是一种癌症.铜铜铜铜铜铜类蛋白质是类蛋白质中的一种.皮质到介质细胞的转变 (EMT)系统生物学系统生物学

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