A Smad3-PTEN regulatory loop controls proliferation and apoptotic responses to TGF-β in mouse endometrium

Visualitza/ Obre
Data de publicació
2017-05-19Autor/a
Felip, Isidre
Dosil Garcia, Maria Alba
Vigezzi, Lucia
Mirantes Barbeito, Cristina
Navaridas Fernández de Bobadilla, Raúl
Santacana Espasa, Maria
Llobet Navàs, David
Yoshimura, Akihiko
Nomura, Masatoshi
Citació recomanada
Eritja Sánchez, Núria;
Felip, Isidre;
Dosil Garcia, Maria Alba;
Vigezzi, Lucia;
Mirantes Barbeito, Cristina;
Yeramian Hakim, Andree;
...
Dolcet Roca, Xavier.
(2017)
.
A Smad3-PTEN regulatory loop controls proliferation and apoptotic responses to TGF-β in mouse endometrium.
Cell Death and Differentiation, 2017, vol. 24, núm. 8, p. 1443-1458.
https://doi.org/10.1038/cdd.2017.73.
Metadades
Mostra el registre d'unitat completResum
The TGF-β/Smad and the PI3K/AKT signaling pathways are important regulators of proliferation and apoptosis, and their alterations lead to cancer development. TGF-β 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-β/Smad and PI3K/AKT signaling pathways. We demonstrate that TGF-β 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-β-induced PTEN expression in endometrial cells, resulting in a blockade of TGF-β-induced apoptosis and an enhancement of cell proliferation. Likewise Smad3 deletion, PTEN knockout prevents TGF-β-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-β.