دورية أكاديمية
Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
| العنوان: | Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment |
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| المؤلفون: | Jei-Ming Peng, Wei-Yu Chen, Jai-Hong Cheng, Jia-Wun Luo, Hong-Tai Tzeng |
| المصدر: | Cancers, Vol 13, Iss 22, p 5648 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | invasive leading cells, TGF-β1, actin cytoskeleton remodeling, vimentin intermediate filament networks, cell detachment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Detachment of cancer cells is the first step in tumor metastasis and malignancy. However, studies on the balance of initial tumor anchoring and detachment are limited. Herein, we revealed that the regulation of cytoskeleton proteins potentiates tumor detachment. The blockage of TGF-β1 using neutralizing antibodies induced cancer cell detachment in the Boyden chamber and 3D in-gel spheroid models. Moreover, treatment with latrunculin B, an actin polymerization inhibitor, enhanced cell dissociation by abolishing actin fibers, indicating that TGF-β1 mediates the formation of actin stress fibers, and is likely responsible for the dynamics of anchoring and detachment. Indeed, latrunculin B disrupted the formation of external TGF-β1-induced actin fibers and translocation of intracellular vinculin, a focal adhesion protein, resulting in the suppression of cell adhesion. Moreover, the silencing of vimentin substantially reduced cell adhesion and enhanced cell detachment, revealing that cell adhesion and focal adhesion protein translocation stimulated by TGF-β1 require vimentin. Using the 3D in-gel spheroid model, we found that latrunculin B suppressed the cell adhesion promoted by external TGF-β1, increasing the number of cells that penetrated the Matrigel and detached from the tumor spheres. Thus, cytoskeleton remodeling maintained the balance of cell anchoring and detachment, and the TGF-β1/vimentin/focal adhesion protein assembly axis was involved in the control dynamics of initial tumor detachment. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2072-6694 35520264 |
| Relation: | https://www.mdpi.com/2072-6694/13/22/5648; https://doaj.org/toc/2072-6694 |
| DOI: | 10.3390/cancers13225648 |
| URL الوصول: | https://doaj.org/article/355202647d7743a9885614105910abc5 |
| رقم الأكسشن: | edsdoj.355202647d7743a9885614105910abc5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20726694 35520264 |
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| DOI: | 10.3390/cancers13225648 |