التفاصيل البيبلوغرافية
| العنوان: |
The laminin-keratin link shields the nucleus from mechanical deformation and signalling |
| المؤلفون: |
Kechagia, Zanetta, Sáez, Pablo, Gómez-González, Manuel, Canales, Brenda, Viswanadha, Srivatsava, Zamarbide, Martín, Andreu, Ion, Koorman, Thijs, Beedle, Amy E M, Elosegui-Artola, Alberto, Derksen, Patrick W B, Trepat, Xavier, Arroyo, Marino, Roca-Cusachs, Pere |
| المساهمون: |
Pathologie Groep Derksen, Cancer |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
Journal Article |
| الوصف: |
The mechanical properties of the extracellular matrix dictate tissue behaviour. In epithelial tissues, laminin is a very abundant extracellular matrix component and a key supporting element. Here we show that laminin hinders the mechanoresponses of breast epithelial cells by shielding the nucleus from mechanical deformation. Coating substrates with laminin-111-unlike fibronectin or collagen I-impairs cell response to substrate rigidity and YAP nuclear localization. Blocking the laminin-specific integrin β4 increases nuclear YAP ratios in a rigidity-dependent manner without affecting the cell forces or focal adhesions. By combining mechanical perturbations and mathematical modelling, we show that β4 integrins establish a mechanical linkage between the substrate and keratin cytoskeleton, which stiffens the network and shields the nucleus from actomyosin-mediated mechanical deformation. In turn, this affects the nuclear YAP mechanoresponses, chromatin methylation and cell invasion in three dimensions. Our results demonstrate a mechanism by which tissues can regulate their sensitivity to mechanical signals. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1476-1122 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/450231Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/450231Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.AE075429 |
| قاعدة البيانات: |
BASE |
