PAX3-FOXO1融合基因减少横纹肌肉瘤中细胞- ecm相互作用和TGFβ信号传导。

IF 7.4 1区生物学 Q1 CELL BIOLOGY

Journal of Cell Biology Pub Date : 2025-06-30 DOI:10.1083/jcb.202408155

Antonios Chronopoulos,Ivan Chavez,Chandra Kaladhar Vemula,Nikhil Mittal,Vic Zamloot,Yuanzhong Pan,Sangyoon J Han,JinSeok Park

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引用次数: 0

摘要

我们发现FPRMS中与细胞- ecm相互作用和tgf - β信号传导相关的基因下调。我们利用共聚焦反射显微镜评估ECM重塑，并利用活细胞传感器定量评估TGFβ信号传导，证实了TGFβ信号传导增强FNRMS中细胞-ECM相互作用。我们还发现PAX3-FOXO1增加NOS1表达，刺激一氧化氮合成，从而抑制TGFβ信号传导并减少细胞- ecm相互作用。我们认为pax3 - fox01通过抑制细胞-ECM相互作用重编程ECM锚定依赖性。融合基因可以通过靶向破坏细胞- ecm相互作用或tgf - β信号传导来确定对生长抑制的敏感性。减少锚定依赖的基因可能允许细胞在循环中存活，并提高FPRMS的转移潜力。

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The PAX3-FOXO1 fusion gene reduces cell-ECM interactions and TGFβ signaling in rhabdomyosarcoma.

We identify downregulation of genes related to cell-ECM interactions and TGFβ signaling in FPRMS. We confirm that TGFβ signaling enhances cell-ECM interactions in FNRMS, utilizing confocal reflection microscopy to assess ECM remodeling, and a live-cell sensor to quantitatively assess TGFβ signaling. We also show that PAX3-FOXO1 increases NOS1 expression, stimulating nitric oxide synthesis, which inhibits TGFβ signaling and reduces cell-ECM interactions. We suggest that PAX3-FOXO1 reprograms ECM anchorage dependence by suppressing cell-ECM interactions. The fusion gene can determine sensitivity to growth inhibition via targeted disruption of cell-ECM interactions or TGFβ signaling. Reduced anchorage reliance by the gene may allow cells to survive in circulation and enhance FPRMS metastatic potential.

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来源期刊

Journal of Cell Biology 生物-细胞生物学

CiteScore

12.60

自引率

2.60%

发文量

213

审稿时长

1 months

期刊介绍： The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.