دورية أكاديمية
Lack of extracellular matrix switches TGF-β induced apoptosis of endometrial cells to epithelial to mesenchymal transition
| العنوان: | Lack of extracellular matrix switches TGF-β induced apoptosis of endometrial cells to epithelial to mesenchymal transition |
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| المؤلفون: | Anna Ruiz-Mitjana, Raúl Navaridas, Maria Vidal-Sabanés, Aida Perramon-Güell, Andree Yeramian, Isidre Felip, Núria Eritja, Joaquim Egea, Mario Encinas, Xavier Matias-Guiu, Xavier Dolcet |
| المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-19 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract The extracellular matrix and the correct establishment of epithelial cell polarity plays a critical role in epithelial cell homeostasis and cell polarity. In addition, loss of tissue structure is a hallmark of carcinogenesis. In this study, we have addressed the role of extracellular matrix in the cellular responses to TGF-β. It is well known that TGF-β is a double-edged sword: it acts as a tumor suppressor in normal epithelial cells, but conversely has tumor-promoting effects in tumoral cells. However, the factors that determine cellular outcome in response to TGF-β remain controversial. Here, we have demonstrated that the lack of extracellular matrix and consequent loss of cell polarity inhibits TGF-β-induced apoptosis, observed when endometrial epithelial cells are polarized in presence of extracellular matrix. Rather, in absence of extracellular matrix, TGF-β-treated endometrial epithelial cells display features of epithelial-to-mesenchymal transition. We have also investigated the molecular mechanism of such a switch in cellular response. On the one hand, we found that the lack of Matrigel results in increased AKT signaling which is sufficient to inhibit TGF-β-induced apoptosis. On the other hand, we demonstrate that TGF-β-induced epithelial-to-mesenchymal transition requires ERK and SMAD2/3 activation. In summary, we demonstrate that loss of cell polarity changes the pro-apoptotic function of TGF-β to tumor-associated phenotype such as epithelial-to-mesenchymal transition. These results may be important for understanding the dual role of TGF-β in normal versus tumoral cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://doaj.org/toc/2045-2322Test |
| DOI: | 10.1038/s41598-022-18976-1 |
| الوصول الحر: | https://doaj.org/article/f38b438a650b4c409f3101a0c6d92387Test |
| رقم الانضمام: | edsdoj.f38b438a650b4c409f3101a0c6d92387 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-022-18976-1 |