H-Ras Transformation of Mammary Epithelial Cells Induces ERK-Mediated Spreading on Low Stiffness Matrix
| Autor: | Yang-Hsun Hou, Christopher M. Plunkett, Jesse K. Placone, Gillian Grennan, Adam J. Engler, Aditya Kumar, Jaime Yrastorza |
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| Rok vydání: | 2020 |
| Předmět: |
MAPK/ERK pathway
Epithelial-Mesenchymal Transition Population Medical Biotechnology Biomedical Engineering Pharmaceutical Science 02 engineering and technology 010402 general chemistry H-ras 01 natural sciences Article Biomaterials microtubules Medicinal and Biomolecular Chemistry breast cancer Microtubule Transforming Growth Factor beta Myosin matrix stiffness medicine education Transcription factor Basement membrane education.field_of_study Chemistry Epithelial Cells 021001 nanoscience & nanotechnology 0104 chemical sciences Cell biology medicine.anatomical_structure Self-healing hydrogels Mechanosensitive channels gene-material interactions 0210 nano-technology Transcription Factors |
| Zdroj: | Advanced healthcare materials, vol 9, iss 8 Adv Healthc Mater |
| Popis: | Oncogenic transformation of mammary epithelial cells (MECs) is a critical step in epithelial-to-mesenchymal transition (EMT), but evidence also shows that MECs undergo EMT with increasing matrix stiffness; the interplay of genetic and environmental effects on EMT is not clear. To understand their combinatorial effects on EMT, pre-malignant MCF10A and isogenic Ras-transformed MCF10AT were cultured on polyacrylamide gels ranging from normal mammary stiffness, ~150 Pascals (Pa), to tumor stiffness, ~5700 Pa. Though cells spread on stiff hydrogels independent of transformation, only 10AT cells exhibited heterogeneous spreading behavior on soft hydrogels. Within this mixed population, spread cells exhibited an elongated, mesenchymal-like morphology, disrupted localization of the basement membrane, and nuclear localization of the EMT transcription factor TWIST1. MCF10AT spreading is not driven by typical mechanosensitive pathways including YAP and TGFβ or by myosin contraction. Rather, ERK activation induced spreading of MCF10AT cells on soft hydrogels and required dynamic microtubules. These findings indicate the importance of oncogenic signals, and their hierarchy with substrate mechanics, in regulating MEC EMT. |
| Databáze: | OpenAIRE |
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