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

dc.contributor.authorEritja Sánchez, Núria
dc.contributor.authorFelip, Isidre
dc.contributor.authorDosil Garcia, Maria Alba
dc.contributor.authorVigezzi, Lucia
dc.contributor.authorMirantes Barbeito, Cristina
dc.contributor.authorYeramian Hakim, Andree
dc.contributor.authorNavaridas Fernández de Bobadilla, Raúl
dc.contributor.authorSantacana Espasa, Maria
dc.contributor.authorLlobet Navàs, David
dc.contributor.authorYoshimura, Akihiko
dc.contributor.authorNomura, Masatoshi
dc.contributor.authorEncinas Martín, Mario
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorDolcet Roca, Xavier
dc.date.accessioned2018-06-14T08:46:55Z
dc.date.available2018-06-14T08:46:55Z
dc.date.issued2017-05-19
dc.identifier.issn1350-9047
dc.identifier.urihttp://hdl.handle.net/10459.1/63501
dc.description.abstractThe 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.
dc.description.sponsorshipSupported by grants SAF2016-80157-R from Ministerio de Economía y Competitividad, PI13/00263 and PI13/01701 from Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III cofinanciado por Fondo Europeo de Desarrollo Regional (FEDER) (“Una manera de hacer Europa”), Red Temática de investigación en Cáncer RD12/0036/0013 and Red de Oncología (CIBERONC). Grups consolidats de la Generalitat de Catalunya (2009SGR794), Fundació La Marató de TV3, Grupos estables AECC, Catalunya contra el cáncer and programa de intensificación de la investigación, Instituto Carlos III.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relationMINECO/PN2013-2016/SAF2016-80157-R
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1038/cdd.2017.73
dc.relation.ispartofCell Death and Differentiation, 2017, vol. 24, núm. 8, p. 1443-1458
dc.rights(c) Nature Publishing Group, 2017
dc.subjectApoptosi
dc.titleA Smad3-PTEN regulatory loop controls proliferation and apoptotic responses to TGF-β in mouse endometrium
dc.title.alternativeSMAD3-PTEN crosstalk regulates TGF-β responses
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2018-06-14T08:46:55Z
dc.identifier.idgrec025785
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1038/cdd.2017.73


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