التفاصيل البيبلوغرافية
| العنوان: |
Endometrial PTEN Deficiency Leads to SMAD2/3 Nuclear Translocation |
| المؤلفون: |
Núria Eritja, Raúl Navaridas, Anna Ruiz-Mitjana, Maria Vidal-Sabanés, Joaquim Egea, Mario Encinas, Xavier Matias-Guiu, Xavier Dolcet |
| المصدر: |
Cancers; Volume 13; Issue 19; Pages: 4990 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| 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. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Methods and Technologies Development; https://dx.doi.org/10.3390/cancers13194990Test |
| DOI: |
10.3390/cancers13194990 |
| الإتاحة: |
https://doi.org/10.3390/cancers13194990Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.2C95342A |
| قاعدة البيانات: |
BASE |
