通过不同的转录组机制,DDR2信号和机械感知调节神经母细胞瘤细胞命运
Theadora Vessella1, Steven Xiang2, Cong Xiao3,4
1Department of Chemical Engineering, Worcester Polytechnic Institute, MA, USA.
FEBS open bio
|March 27, 2024
概括
通过迪斯科伊丁域受体2 (DDR2) 传递的细胞外矩阵 (ECM) 信号和ECM的刚性都会影响癌细胞的增殖. DDR2下调改变了基因表达,而性通过不同的,潜在的非转录性机制影响了细胞命运.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 生物物理学的生物物理.
背景情况:
- 细胞外基质 (ECM) 在通过细胞表面受体,如迪斯科伊丁域受体2 (DDR2) 调节癌症进展方面发挥着至关重要的作用.
- 癌细胞具有机械感知能力,检测ECM硬度,这是一个在致癌过程中经常改变的因素.
- 癌细胞行为中的DDR2信号和ECM机械感知之间的相互作用在很大程度上仍未被探索.
研究的目的:
- 调查原激活的DDR2信号和ECM硬度诱导的机械感应是否会对癌细胞行为产生类似的影响.
- 为了确定这两个ECM介导的途径是否通过类似的分子机制运作.
- 阐明癌细胞中DDR2信号和机械感知之间的潜在交叉声.
主要方法:
- 大量RNA测序 (RNA-seq) 在人类SH-SY5Y神经母细胞瘤细胞上进行,这些细胞在原涂层基板上培养.
- 实验操作包括DDR2下调 (Knockdown) 和不同的基板刚度.
- 分析了细胞反应,包括增殖,衰老和转录组变化.
主要成果:
- DDR2降低调节显著改变了细胞转录组,影响了参与细胞分裂和分化的基因,并将细胞命运从增殖转向衰老.
- 基质刚度增加减少了细胞增殖,但令人惊的是,并没有通过RNA-seq.诱导可检测的转录基因变化.
- DDR2 knockdown调节了细胞对基质刚性的反应,这表明DDR2信号与机械感知之间存在交叉声.
结论:
- 在癌细胞中,ECM可以激活DDR2信号和机械感知,以协调细胞命运.
- 这些途径可能通过不同的机制运作,可能独立于基因表达变化,为癌症进展提供了新的见解.
- 了解这种交叉通话提供了关于ECM如何影响癌细胞行为的新机制性见解.
相关概念视频
03:14Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
01:19Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K