A Smad3-PTEN regulatory loop controls proliferation and apoptotic responses to TGF-ß in mouse endometrium.
Cell Death Differ
; 24(8): 1443-1458, 2017 08.
Article
en En
| MEDLINE
| ID: mdl-28524854
ABSTRACT
The TGF-ß/Smad and the PI3K/AKT signaling pathways are important regulators of proliferation and apoptosis, and their alterations lead to cancer development. TGF-ß acts as a tumor suppressor in premalignant cells, but it is a tumor promoter for cancerous cells. Such dichotomous actions are dictated by different cellular contexts. Here, we have unveiled a PTEN-Smad3 regulatory loop that provides a new insight in the complex cross talk between TGF-ß/Smad and PI3K/AKT signaling pathways. We demonstrate that TGF-ß triggers apoptosis of wild-type polarized endometrial epithelial cells by a Smad3-dependent activation of PTEN transcription, which results in the inhibition of PI3K/AKT signaling pathway. We show that specific Smad3 knockdown or knockout reduces basal and TGF-ß-induced PTEN expression in endometrial cells, resulting in a blockade of TGF-ß-induced apoptosis and an enhancement of cell proliferation. Likewise Smad3 deletion, PTEN knockout prevents TGF-ß-induced apoptosis and increases cell proliferation by increasing PI3K/AKT/mTOR signaling. In summary, our results demonstrate that Smad3-PTEN signaling axis determine cellular responses to TGF-ß.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
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Endometrio
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Células Epiteliales
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Fosfohidrolasa PTEN
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Proteína smad3
Límite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Año:
2017
Tipo del documento:
Article
País de afiliación:
España