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基质硬度驱动核变形和核纤层 A/C 张力依赖性 YAP 核定位的下降。

Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization.

机构信息

Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA.

Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA.

出版信息

Nat Commun. 2024 Nov 22;15(1):10151. doi: 10.1038/s41467-024-54577-4.

Abstract

Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells.

摘要

细胞外基质(ECM)的硬度通过改变基因表达来影响癌细胞的命运。先前的研究表明,刚性诱导的核变形可能通过 YAP 核定位来调节基因表达。我们研究了核层在这个过程中的作用。我们表明,核层表现出力学阈值行为:一旦展开,核层就不可延展。计算模型预测,展开的核层处于张紧状态,这可以使用核层张力传感器来证实。核层的展开是由于细胞在坚硬的 ECM 上扩展时核的扁平化引起的。核纤层 A/C 的敲低消除了核表面张力并减少了核 YAP 的定位。这些发现表明,细胞中的核变形符合核滴模型,并揭示了核纤层 A/C 张力在控制癌细胞中 YAP 定位中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/662f/11584751/372aac372d38/41467_2024_54577_Fig1_HTML.jpg

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