化的瘤微环境通过整合蛋白信号传递增强乳腺癌中的围神经入侵
Bing Han1, Xin Guan1, Mingyue Ma1
1Departments of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun City, Jilin Province, 130021, People's Republic of China.
Cellular oncology (Dordrecht, Netherlands)
|November 28, 2023
概括
刚性瘤微环境通过激活整合蛋白β1-FAK-YAP信号来促进乳腺癌周围神经入侵 (PNI). 这一途径增强了癌细胞的侵入性和神经营养效应,促进了PNI.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 瘤微环境研究 研究
背景情况:
- 神经透是各种癌症瘤进展的关键因素,包括乳腺癌 (BRCA).
- 在BRCA中观察到周围神经侵入 (PNI),但其潜在的调节机制仍然不太清楚.
- 了解PNI机制对于开发有效的癌症疗法至关重要.
研究的目的:
- 为了研究调节乳腺癌 (BRCA) 中围神经侵入 (PNI) 的分子机制.
- 探索细胞外基质 (ECM) 在BRCA中促进PNI的作用.
- 为了确定BRCA中PNI的潜在治疗点.
主要方法:
- 对BRCA样本的癌症基因组图谱 (TCGA) 的RNA测序数据的分析.
- 免疫组织化学染色 (α-SMA,Sirius红色,Masson三色) 用于评估ECM组件.
- 在体外测试中使用矩阵凝和背部根腺 (DRG) 共同培养来监测癌细胞的侵入性.
- 西方涂抹,qRT-PCR和ELISA以阐明分子信号通路.
主要成果:
- 在ECM组成和BRCA中的PNI状态之间发现了显著的关联.
- 更硬的矩阵增强了BRCA细胞的侵入性和对DRG神经元的神经变效应.
- 鉴定出因特林β1 (ITGB1) 是一种关键受体,它调解了矩阵刚性的影响.
- 整合素β1-FAK-YAP信号通路的激活与侵入性和神经营养因子表达 (NGF) 的增加有关.
结论:
- 硬化的细胞外基质通过整体蛋白β1-FAK-YAP信号级联促进BRCA中的PNI.
- 这种机制调节前转移性和神经变性基因,促进癌细胞沿神经线的入侵.
- 这些发现为BRCA中PNI提供了新的见解,并建议潜在的神经向治疗策略.
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