Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment
| العنوان: | Dysregulation of Cytoskeleton Remodeling Drives Invasive Leading Cells Detachment |
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| المؤلفون: | Wei-Yu Chen, Jei-Ming Peng, Jia-Wun Luo, Hong-Tai Tzeng, Jai-Hong Cheng |
| المصدر: | Cancers Cancers, Vol 13, Iss 5648, p 5648 (2021) Volume 13 Issue 22 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Matrigel, biology, Chemistry, invasive leading cells, actin cytoskeleton remodeling, vimentin intermediate filament networks, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Vimentin, macromolecular substances, Vinculin, cell detachment, Article, Cell biology, Focal adhesion, Oncology, TGF-β1, biology.protein, Cell adhesion, Cytoskeleton, RC254-282, Actin, Intracellular |
| الوصف: | Simple Summary Detachment of cancer cells is the first step in tumor metastasis and malignancy. Our results showed that the TGF-β1/vimentin/focal adhesion protein assembly axis was involved in the control of the dynamics of initial tumor detachment under adequate nutrition, based on the Boyden chamber and 3D in-gel spheroid analysis. Abstract 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afd88c0c82c45800ec3b6f909abba2aa https://pubmed.ncbi.nlm.nih.gov/34830801 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....afd88c0c82c45800ec3b6f909abba2aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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