The PAX3-FOXO1 Fusion Gene Reduces cell-ECM Interactions and TGFβ Signaling in rhabdomyosarcoma
Document Type
Article
Publication Date
7-7-2025
Department
Department of Biomedical Engineering
Abstract
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.
Publication Title
The Journal of cell biology
Recommended Citation
Chronopoulos, A.,
Chavez, I.,
Vemula, C. K.,
Mittal, N.,
Zamloot, V.,
Han, S. J.,
&
et. al.
(2025).
The PAX3-FOXO1 Fusion Gene Reduces cell-ECM Interactions and TGFβ Signaling in rhabdomyosarcoma.
The Journal of cell biology,
224(7), e202408155.
http://doi.org/10.1083/jcb.202408155
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p2/1824
Publisher's Statement
© 2025 Chronopoulos et al.