产生ADAM12基因的基底域内主体结合β1整体蛋白并增强与癌症相关的细胞外矩阵蛋白的表达
Kasper J Mygind1, Denise Nikodemus1, Sebastian Gnosa1
1Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
International journal of molecular sciences
|June 19, 2024
概括
由ADAM12生成的基因ectodomain促进癌细胞迁移和细胞外矩阵重塑,有助于脱细胞形成. 这项研究揭示了一个反循环,涉及ADAM12,基因分泌和TGFβ在癌症进展中的信号传递.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 侵袭性癌症的标志性特征 - - 脱形成症,涉及复杂的蛋白质动态.
- 作为一种膜受体的Basigin可以作为一种可溶性ectodomain脱落.
- 升的可溶性巴西金与癌症预后不佳相关.
研究的目的:
- 为了研究ADAM12生成的基因ectodomain在癌症进展中的作用.
- 阐明可溶性巴西金对瘤微环境的影响机制.
主要方法:
- 再组合基因ectodomain与β1整合素的结合试验.
- 关于癌细胞迁移和细胞外基质降解的体外和体内研究.
- 在瘤中分析细胞外矩阵蛋白表达 (纤维蛋白,原蛋白5型).
主要成果:
- 基因ectodomain与β1整合素结合刺激了凝降解和癌细胞迁移.
- 确定了对矩阵金属蛋白酶 (MMP) 和β1-整合素的依赖性.
- 在表达ADAM12的瘤中观察到增加了5型原体沉积,模仿了脱.
结论:
- 通过ECM重塑,ADAM12生成的原始细胞域有助于脱质形成.
- 一个涉及ADAM12的反循环,基因脱落,TGFβ信号传递和ECM重塑,调节了desmoplasia.
- 溶性巴西金可能在脱质性癌症中代表治疗标.
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