| First Author | Eritja N | Year | 2017 |
| Journal | Cell Death Differ | Volume | 24 |
| Issue | 8 | Pages | 1443-1458 |
| PubMed ID | 28524854 | Mgi Jnum | J:268124 |
| Mgi Id | MGI:6269871 | Doi | 10.1038/cdd.2017.73 |
| Citation | Eritja N, et al. (2017) A Smad3-PTEN regulatory loop controls proliferation and apoptotic responses to TGF-beta in mouse endometrium. Cell Death Differ 24(8):1443-1458 |
| abstractText | The TGF-beta/Smad and the PI3K/AKT signaling pathways are important regulators of proliferation and apoptosis, and their alterations lead to cancer development. TGF-beta 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-beta/Smad and PI3K/AKT signaling pathways. We demonstrate that TGF-beta 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-beta-induced PTEN expression in endometrial cells, resulting in a blockade of TGF-beta-induced apoptosis and an enhancement of cell proliferation. Likewise Smad3 deletion, PTEN knockout prevents TGF-beta-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-beta. |
