Academic Journal
Endometrial PTEN Deficiency Leads to SMAD2/3 Nuclear Translocation
| العنوان: | Endometrial PTEN Deficiency Leads to SMAD2/3 Nuclear Translocation |
|---|---|
| المؤلفون: | Eritja Sánchez, Núria, Navaridas Fernández de Bobadilla, Raúl, Ruiz Mitjana, Anna, Vidal Sabanés, Maria, Egea Navarro, Joaquim, Encinas Martín, Mario, Matias-Guiu, Xavier, Dolcet Roca, Xavier |
| بيانات النشر: | MDPI |
| سنة النشر: | 2021 |
| المجموعة: | Universitat de Lleida: Repositori Obert UdL |
| مصطلحات موضوعية: | PTEN, TGF-β, SMAD2/3, Endometrial cancer |
| الوصف: | TGF-β has a dichotomous function, acting as tumor suppressor in premalignant cells but as a tumor promoter for cancerous cells. These contradictory functions of TGF-β are caused by different cellular contexts, including both intracellular and environmental determinants. The TGF-β/SMAD and the PI3K/PTEN/AKT signal transduction pathways have an important role in the regulation of epithelial cell homeostasis and perturbations in either of these two pathways' contributions to endometrial carcinogenesis. We have previously demonstrated that both PTEN and SMAD2/3 display tumor-suppressive functions in the endometrium, and genetic ablation of either gene results in sustained activation of PI3K/AKT signaling that suppresses TGF-β-induced apoptosis and enhances cell proliferation of mouse endometrial cells. However, the molecular and cellular effects of PTEN deficiency on TGF-β/SMAD2/3 signaling remain controversial. Here, using an in vitro and in vivo model of endometrial carcinogenesis, we have demonstrated that loss of PTEN leads to a constitutive SMAD2/3 nuclear translocation. To ascertain the function of nuclear SMAD2/3 downstream of PTEN deficiency, we analyzed the effects of double deletion PTEN and SMAD2/3 in mouse endometrial organoids. Double PTEN/SMAD2/3 ablation results in a further increase of cell proliferation and enlarged endometrial organoids compared to those harboring single PTEN, suggesting that nuclear translocation of SMAD2/3 constrains tumorigenesis induced by PTEN deficiency. ; This research was supported by grants SAF2016-80157-R and PID2019-104734RB-I00 from Spanish Ministerio de Ciencia, Innovación y Universidades, Grupos estables de la Asociación Española Contra el Cancer, AECC |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| Relation: | info:eu-repo/grantAgreement/MINECO//SAF2016-80157-R/ES/; Reproducció del document publicat a : https://doi.org/10.3390/cancers13194990; Cancers, 2021, vol. 13, núm. 19, p. 4990; https://doi.org/10.3390/cancers13194990; http://hdl.handle.net/10459.1/72131 |
| DOI: | 10.3390/cancers13194990 |
| الاتاحة: | http://hdl.handle.net/10459.1/72131 https://doi.org/10.3390/cancers13194990 |
| Rights: | cc-by (c) autors, 2021 ; info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.B50248C3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20726694 |
|---|---|
| DOI: | 10.3390/cancers13194990 |