The study of ECM hardness and mechanical pressure promoting TSCC progression by activating RET in a 4D culture system

This study developed a 4D dynamic culture model (a 3D hydrogel system integrated with time-dependent mechanical stimuli via magnetic nanoparticles) to simulate tongue movement and investigate the roles of ECM stiffness and mechanical pressure in tongue squamous cell carcinoma (TSCC) progression. The...

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Bibliographic Details
Main Authors: Yuezhu Wang, Yibo Wang, Yuhang Xing, Guangping Jing
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials & Design
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Online Access:http://www.sciencedirect.com/science/article/pii/S026412752501010X
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Summary:This study developed a 4D dynamic culture model (a 3D hydrogel system integrated with time-dependent mechanical stimuli via magnetic nanoparticles) to simulate tongue movement and investigate the roles of ECM stiffness and mechanical pressure in tongue squamous cell carcinoma (TSCC) progression. The model demonstrated excellent biocompatibility and stability. Results showed that ECM stiffness and mechanical pressure significantly enhanced TSCC cell proliferation, migration, and invasion by activating the RET/AKT/GSK-3β/β-catenin/c-Myc pathway. Specifically, mechanical pressure induced RET phosphorylation at Y1062, triggering downstream signaling. Silencing RET or inhibiting PI3K/AKT suppressed these effects. The 4D model provides a physiologically relevant platform for studying TSCC mechanobiology, highlighting RET as a potential therapeutic target. These findings underscore the importance of mechanical cues in TSCC progression and offer insights for novel treatment strategies.
ISSN:0264-1275