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: | Ruiz Mitjana, Anna, Navaridas Fernández de Bobadilla, Raúl, Vidal Sabanés, Maria, Perramon Güell, Aida, Yeramian Hakim, Andree, Felip Nogués, Isidre, Eritja Sánchez, Núria, Egea Navarro, Joaquim, Encinas Martín, Mario, Matias-Guiu, Xavier, Dolcet Roca, Xavier |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2022 |
| المجموعة: | Universitat de Lleida: Repositori Obert UdL |
| مصطلحات موضوعية: | Apoptosis (drug effects), Carcinogenesis, Endometrium, Transforming Growth Factor beta |
| الوصف: | 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. ; Supported by grants and PID2019-104734RB-I00 from Spanish Ministerio de Ciencia, Innovación y Universi-dades, Grupos estables de la Asociación Española Contra el Cancer, AECC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104734RB-I00/ES/DESCIFRANDO REDES DE SEÑALIZACION EN EL CANCER DE ENDOMETRIO: PAPEL DEL MICRORNA-424(322)%2F503 NEOPLASIAS ENDOMETRIALES Y SU REGULACION POR LAS VIAS PI3K%2FAKT Y TGF-BETA%2FSMAD/; Reproducció del document publicat a: https://doi.org/10.1038/s41598-022-18976-1Test; Scientific Reports, 2022, vol. 12, núm. 1; http://hdl.handle.net/10459.1/83910Test; https://doi.org/10.1038/s41598-022-18976-1Test |
| DOI: | 10.1038/s41598-022-18976-1 |
| الإتاحة: | https://doi.org/10.1038/s41598-022-18976-1Test http://hdl.handle.net/10459.1/83910Test |
| حقوق: | cc-by (c) Authors, 2022 ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.C4CCBBDB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-022-18976-1 |