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Matrix stiffness regulates epithelial-mesenchymal transition via cytoskeletal remodeling and MRTF-A translocation in osteosarcoma cells.
Journal of the Mechanical Behavior of Biomedical Materials ( IF 3.3 ) Pub Date : 2018-10-16 , DOI: 10.1016/j.jmbbm.2018.10.012
Jun Dai 1 , Liang Qin 1 , Yan Chen 1 , Huan Wang 1 , Guanlin Lin 1 , Xiao Li 1 , Hui Liao 1 , Huang Fang 1
Affiliation  

Matrix stiffness is known to alter cellular behaviors in various biological contexts. Previous investigations have shown that epithelial–mesenchymal transition (EMT) promotes the progression and invasion of tumor. Mechanical signaling is identified as a regulator of EMT. However, the molecular mechanisms underlying the influence exerted by matrix stiffness on EMT in osteosarcoma remains largely unknown. Using polyacrylamide hydrogel model, we investigate the effects of matrix stiffness on EMT and migration in osteosarcoma. Our data indicates that high matrix stiffness regulates cell morphology and promotes EMT and migration in osteosarcoma MG63 cell line in vitro. Notably, matrix stiffness promotes polymerization of actin and nuclear accumulation of myocardin-related transcription factor A (MRTF-A). Furthermore, inhibiting MRTF-A by CCG 203971 significantly reduces EMT and migration on rigid gels. These data suggest that matrix stiffness of the tumor microenvironment actively regulate osteosarcoma EMT and migration through cytoskeletal remodeling and translocation of MRTF-A, which may contribute to cancer progression.



中文翻译:

基质刚度通过骨肉瘤细胞中的细胞骨架重塑和MRTF-A易位来调节上皮-间质转化。

已知基质刚度会改变各种生物学环境下的细胞行为。先前的研究表明,上皮-间质转化(EMT)促进了肿瘤的进展和侵袭。机械信号被识别为EMT的调节器。然而,由基质刚度对骨肉瘤EMT产生影响的分子机制仍是未知之数。使用聚丙烯酰胺水凝胶模型,我们调查基质硬度对骨肉瘤EMT和迁移的影响。我们的数据表明,高基质刚度可调节细胞形态,并在体外促进骨肉瘤MG63细胞系中的EMT和迁移。值得注意的是,基质刚度促进肌动蛋白的聚合和心肌相关转录因子A(MRTF-A)的核积累。此外,CCG 203971抑制MRTF-A可以显着降低EMT和在刚性凝胶上的迁移。这些数据表明,肿瘤微环境的基质刚度通过细胞骨架重塑和MRTF-A易位而主动调节骨肉瘤EMT和迁移,这可能有助于癌症的进展。

更新日期:2018-10-16
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