自克林TGFβ2强制在尤文肉瘤中强制转录混合细胞状态
Emma D Wrenn1, Jacob C Harris1, April A Apfelbaum2
1Ben Towne Center for Childhood Cancer & Blood Disorders Research, Seattle Children's Research Institute, Seattle, WA, USA.
Science advances
|January 21, 2026
概括
转化生长因子-β (TGFβ) 信号驱动了尤文肉瘤 (EwS) 细胞中的混合状态,促进了它们的入侵和转移. 这种反循环涉及TGFβ2分泌和持续的途径激活,增强细胞外基质沉积.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 与癌症相关的纤维细胞样 (CAF) 细胞通过细胞外基质 (ECM) 沉积促进了尤文肉瘤 (EwS) 的进展.
- 在EWS细胞中,由EWS::FLI1驱动的混合转录状态激活了增殖,同时抑制了间酶体基因.
研究的目的:
- 为了确定EWS细胞中混合转录状态的分子驱动因素.
- 研究转化生长因子-β (TGFβ) 信号在维持这种混合状态和促进转移中的作用.
主要方法:
- 对初级患者瘤和细胞系模型的分析.
- 研究TGFβ信号通路组件,包括TGFBR2表达和TGFβ2分泌.
- 评估TGFβ1和TGFβ2对EWS细胞增殖和侵入的影响.
主要成果:
- 一个涉及TGFβ信号的正反循环诱导并保持混合EWS细胞状态.
- 混合细胞调节TGFBR2并分泌TGFβ2,维持通路激活和ECM沉积.
- TGFβ1和TGFβ2在不影响增殖的情况下促进了EWS细胞的入侵.
结论:
- TGFβ信号传递是EWS细胞中混合转录状态的关键驱动因素.
- 来自瘤和瘤的TGFβ配体通过诱导和维持混合细胞来促进EWS中的转移前表型.
- 准TGFβ通路可能提供抑制EWS转移的治疗策略.
相关概念视频
Autocrine Signaling
52.1K
Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
52.1K
Transcription
155.7K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
155.7K
Transcription Factors
82.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.3K
Hybrid Zones
21.8K
Hybrid zones are narrow regions where two closely related species interact, mate, and produce hybrids. Relative to either parent species, hybrids may possess distinct phenotypic or genetic differences that impact their survival and reproductive success. The genetic variances introduced by hybridization influence species diversity and speciation processes within the hybrid zone.
21.8K
Master Transcription Regulators
7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K
Transcription Elongation Factors
13.5K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
13.5K


